Postoperative Care in Thoracic Surgery A Comprehensive Guide

Editors
Mert Şentürk and Mukadder Orhan Sungur
Postoperative Care in Thoracic Surgery

A Comprehensive Guide
Editors
Mert Şentürk
Department of Anaesthesiology and Intensive Care, Istanbul University, Istanbul
Faculty of Medicine, Istanbul, Turkey
Mukadder Orhan Sungur

Department of Anaesthesiology and Intensive Care, Istanbul University, Istanbul
Faculty of Medicine, Istanbul, Turkey
ISBN 978-3-319-19907-8 e-ISBN 978-3-319-19908-5

DOI 10.1007/978-3-319-19908-5
Library of Congress Control Number: 2017933454
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Dedicated to our families and our beloved departed mentor Prof. Dr. Kutay
Akpir.
Preface
Postoperative care after thoracic surgery is a multidisciplinary challenge.
Obviously, the success of the postoperative care is associated with the success of
the surgical process; however, this correlation is probably much stronger in
thoracic operations. This “multidisciplinary” character can lead sometimes to
some discussions between different disciplines.
This book has several aims: First, and most importantly, it is written to
“comprehend” a concrete point of view to the topic. To achieve this, different
operations (such as esophagectomy, thymectomy) and different patient
populations (such as patients with obstructive pulmonary diseases) have been
included. The content of the book limits itself not only to the postoperative
period, but covers also preoperative assessment and peroperative management of
respiratory and circulatory variables with their relation to a safe and reliable
postoperative multidisciplinary planning and management. Second, it is also
trying to give the reader some connections of theoretical knowledge and
practical approaches. Last but not least, the book is concentrating on a rather
“narrow,” but challenging area and “claims” to be “reference” in this important
topic.
To achieve these aims, the book has some advantages, of which the most
important one was that the authors are some of the most “prominent” thoracic
anesthesiologists. As a matter of fact, I really believe that it is not easy to find
the arguments of so many “experts” of thoracic anesthesia in a book. From this
point of view: Yes, the content is not necessarily “evidence-based” and can
sometimes be an “expert opinion.” But: Yes, these “expert opinions” are also
mostly based on the “evidences,” which have been introduced, explained, and
sometimes debated by these experts. The reader will not only find the “recent
knowledge” and the “guidelines” (which she/he can find elsewhere too), but
she/he will also face some questions about some routine approaches.
The most important challenge was to prevent the “repetitions.” Indeed, the
reader will be addressed to some other chapters within the book. Yet, I have
intentionally permitted some of the repetitions if I believe that the way of the
“expression” was worthy for the reader to understand the argument.
For me, it was a pleasure and honor to edit this book: I just asked my
“friends” whether it is a good idea to write a book about this topic and asked
them to contribute; and yes, they accepted. Personally, I am very happy with the
resulting product. I thank them all, very much. I want to thank also Andrea
Ridolfi and other friends from Springer for the encouragement (and also for their
patience). And, surely, it would be impossible for me to finish this job by myself.
A very hardworking colleague, and a very good friend, Mukadder Orhan Sungur
has coedited this book. Without her help, this book would remain as a dream.
We hope that the reader will share similar feelings with us about the book,
after reading it.
Mert Şentürk
Istanbul, Turkey
2016
Contents
1 What Happens to the Lung During Mechanical Ventilation and One-Lung
Ventilation?
Göran Hedenstierna
2 Where Should I Send My Patient After the Operation?

Lukas Kreienbühl, Tiziano Cassina and Marc Licker
3 Does It Matter How I Ventilate the Patient During the Operation?

Laszlo L. Szegedi
4 Can Postoperative Pulmonary Complications Be Objectively Evaluated?

Marcelo Gama de Abreu, Thomas Kiss, Lluis Gallart and Jaume Canet
5 Fluid Management During and After the Operation: Less Is More or

More Is Less?
Catherine Ashes and Peter Slinger
6 How to Organise the PACU? What to Treat in the PACU?

Mohamed R. El Tahan
7 Should I Blame the Surgeon: Surgical Complications and Surgical

Treatment of the Complications
Jelena Grusina-Ujumaza and Alper Toker
8 Should Every “Myasthenic Thymectomy” Be Sent to ICU?

Zerrin Sungur and Mert Şentürk
9 How About Esophagectomies?

Tamás Végh
10 Do the New Hemodynamic Monitoring Devices Make Sense Compared to

the “Classical” Ones?
Giorgio Della Roca
11 What Are the Specific Challenges in the Postoperative Mechanical

Ventilation After Thoracic Surgery?
Edmond Cohen, Peter Biro and Mert Şentürk
12 Pros and Cons of Non-invasive Ventilation After Thoracic Surgery
Lorenzo Ball, Maddalena Dameri and Paolo Pelosi
13 Lung Surgery and Extracorporeal Oxygenation

Edda M. Tschernko and Clemens Aigner
14 Pneumonia After Thoracic Surgery

Perihan Ergin Özcan and Evren Şentürk
15 When and How Do I Have to Treat the Arrhythmias After Thoracic

Surgery?
Wilhelm Haverkamp and Thomas Hachenberg
16 Management of Antiaggregated and Anticoagulated Patients Scheduled

for Thoracic Surgery: Recommendations for Venous Thromboprophylaxis
Juan V. Llau, Manuel Granell and Mª José Jiménez
17 Pain Management Following Thoracic Surgery

Mukadder Orhan Sungur and Mert Şentürk
18 Rehabilitation for Thoracic Surgical Patients: Why, When, and How

Grégoire Blaudszun, Frédéric Triponez, Pierre-Olivier Bridevaux and
Marc Joseph Licker
19 Perioperative Care of Thoracic Trauma Patient

Kemalettin Koltka
20 Chronic Obstructive Pulmonary Disease and the Postoperative Period

Gary H. Mills
Index
Contributors
Clemens Aigner
Department of Thoracic Surgery, Vienna General Hospital, University of Vienna,
Vienna, Austria
Catherine Ashes
Department of Anaesthetics, St Vincent’s Hospital, Fitzroy, NSW, Australia
Lorenzo Ball
IRCCS AOU San Martino-IST, Department of Surgical Sciences and Integrated
Diagnostics, University of Genoa, Genoa, Italy
Peter Biro
Institute of Anesthesiology, University Hospital Zurich, Zurich, Switzerland
Grégoire Blaudszun
Department of Anaesthesiology, Pharmacology and Intensive Care, Geneva
University Hospitals, Geneva, Switzerland
Pierre-Olivier Bridevaux
Division of Pulmonary Medicine, Geneva University Hospitals, Geneva,
Switzerland
Jaume Canet
Department of Anesthesiology, Hospital Universitari Germans Trias i Pujol,
Universitat Autònoma de Barcelona, Badalona, Spain
Tiziano Cassina
Division of Anesthesiology, University Hospitals of Geneva, Geneva,
Switzerland
Edmond Cohen
Departments of Anesthesiology and Thoracic Surgery, The Icahn School of
Medicine at Mount Sinai, New York, NY, USA
Maddalena Dameri
Mohamed R. El Tahan
Anaesthesiology Department, College of Medicine, University of Dammam,
Dammam, Saudi Arabia
Marcelo Gama de Abreu

Department of Anesthesiology and Intensive Care Therapy, Pulmonary
Engineering Group, University Hospital Carl Gustav Carus, Technische
Universität Dresden, Dresden, Germany
Lluis Gallart
Department of Anesthesiology, Hospital Universitari Germans Trias i Pujol,
Manuel Granell
Department of Anaesthesiology, Critical Care and Pain Relief, General
University Hospital of Valencia, Valencia, Spain
University of Valencia, Valencia, Spain
Catholic University of Valencia, Valencia, Spain
Jelena Grusina-Ujumaza
Paul Stradins University, Riga, Latvia
Department of Thoracic Surgery, Pauls Stradins Clinical University Hospital,
Riga, Latvia
Department of Thoracic Surgery, Group Florence Nightingale Hospitals,
Istanbul, Turkey
Thomas Hachenberg
Department of Anaesthesiology and Intensive Care Medicine, Otto-von-
Guericke University, Magdeburg, Germany
Wilhelm Haverkamp
Department of Cardiology, Charite University Medicine, Berlin, Germany
Göran Hedenstierna
Hedenstierna Laboratory, Department of Medical Sciences, Clinical Physiology,
Uppsala University Hospital, Uppsala, Sweden
Mª José Jiménez
Department of Anaesthesiology, Critical Care and Pain Relief, Hospital Clinic of
Barcelona, Barcelona, Spain
Thomas Kiss
Department of Anesthesiology and Intensive Care Therapy, Pulmonary
Kemalettin Koltka
Department of Anesthesiology and Intensive Care Medicine, Istanbul University,
Istanbul Faculty of Medicine, Istanbul, Turkey
Lukas Kreienbühl
Switzerland
Marc Joseph Licker

Switzerland
Department of Anaesthesiology, Pharmacology, and Intensive Care, Geneva
Juan V. Llau
Department of Anaesthesia and Critical Care, Hospital Clínic, Valencia.
Gary H. Mills
Sheffield Teaching Hospital and University of Sheffield, Sheffield, UK
Perihan Ergin Özcan

Paolo Pelosi
Giorgio Della Roca

Medical University of Udine, Department of Anesthesia and Intensive Care
Medicine of the University of Udine, Udine, Italy
Evren Şentürk
Mert Şentürk
Peter Slinger
Department of Anesthesia, Toronto General Hospital, Toronto, Canada
Mukadder Orhan Sungur

Zerrin Sungur
Laszlo L. Szegedi, MD, PhD

Universitair Ziekenhuis Brussel and Vrije Universiteit Brussel, Brussels,
Belgium
Alper Toker
Department of Thoracic Surgery, Group Florence Nightingale Hospitals,
Istanbul, Turkey
Department of Thoracic Surgery, Istanbul University, Istanbul Faculty of
Medicine, Istanbul, Turkey
Frédéric Triponez
Service of Thoracic and Endocrine Surgery, Geneva University Hospitals,
Geneva, Switzerland
Edda M. Tschernko
Department of Cardiothoracic Anesthesia and Intensive Care Medicine, Vienna
General Hospital, University of Vienna, Vienna, Austria
Tamás Végh
University of Debrecen, Department of Anesthesiology and Intensive Care,
Debrecen, Hungary
Outcomes Research Consortium, Cleveland, OH, USA
Mert Şentürk and Mukadder Orhan Sungur (eds.), Postoperative Care in Thoracic Surgery,
DOI 10.1007/978-3-319-19908-5_1
1. What Happens to the Lung During

Mechanical Ventilation and One-Lung
Ventilation?
Göran Hedenstierna1
(1) Hedenstierna Laboratory, Department of Medical Sciences, Clinical
Physiology, Uppsala University Hospital, Uppsala, Sweden

Göran Hedenstierna
Email: goran.hedenstierna@akademiska.se
1.1 Introduction
Focus of this chapter is on mechanical ventilation of one or both lungs in
connection to thoracic surgery. Morphological and functional changes will be
discussed as well as possible techniques to minimize any impairment. There is
good reason to look for improved ventilator regimes. Despite decades of
experience of the caring of the anesthetized patient, several recent multicenter
studies show considerable incidence of postoperative lung complications. They
may at least in part be attributed to the decreased lung function during
anesthesia. However, how to optimize perioperative ventilator regime has not
been fully agreed upon. Combinations of low tidal volume, recruitment
maneuvers, and positive end-expiratory pressure (PEEP) have been tested, but
recommendations differ between studies [1–3]. In a meta-analysis based on
3,365 patients, the total incidence of postoperative lung injury was similar for
abdominal and thoracic surgery (3.4 % vs 4.3 %) [4]. Patients who developed
postoperative lung injury received ventilation with higher tidal volumes and
lower positive end-expiratory pressure levels, or both, than patients who did not.
Thus, lung-protective mechanical ventilation strategies, as presently used, may
reduce the incidence of postoperative lung injury but uncertainty still remains on
what is optimal ventilation, and more can be done.
Functional residual capacity (FRC) is reduced by 0.8–1.0 L by changing the
body position from upright to supine, and there is a further decrease by 0.4–0.5 L
by the general anesthetic, whether inhaled or given intravenously [5] (except
with ketamine that does not lower tone or FRC [6]). Muscle relaxants will
presumably have similar effects as the anesthetic. As a result, the end-expiratory
lung volume is reduced to close to residual volume.
The decrease in FRC is a likely explanation to the fall in respiratory
compliance and increase in respiratory resistance [7], the former by the reduced
ventilated lung volume and the latter by decreased airway dimensions.
1.2 Airway Closure

During anesthesia, airways may close during expiration and reopen during the
succeeding inspiration. They may even be continuously closed. The closure
occurs because of higher extraluminal than intraluminal airway pressure. Since
pleural pressure is higher in lower dependent than upper, nondependent regions,
airway closure occurs primarily in the dependent lung. It impedes ventilation and
with persisting perfusion causes a ventilation/perfusion mismatch (“low V/Q”)
[8]. The reduced ventilation in the lower half of the lung, as shown in Fig. 1.1,
right panel, is reasonably explained by airway closure. Of similar or perhaps
greater importance is that the continuously closed airways cause resorption
atelectasis, as will be discussed next.
Fig. 1.1 CT scan (left panel) and vertical distributions of ventilation (open squares) and perfusion (closed
circles) in an anesthetized subject (right lower panel). Ventilation and perfusion distributions in a waking
subject are also shown (right upper panel). In the anesthetized subject, atelectasis can be seen in the bottom
of both lungs. Note also that most of the ventilation is distributed to the upper half of the lung and is
decreasing in the lower half until the bottom where the ventilation has ceased. This is different from the
distribution in the waking subject. Perfusion on the other hand increases down the lung, similar to the
waking situation, except for the lowermost part where a certain decrease can be seen. This causes a
considerable ventilation/perfusion mismatch with high V/Q in the upper half of the lung, mimicking dead
space ventilation, and low V/Q and shunt in the lowermost regions
1.3 Formation of Atelectasis

In their classic paper, Bendixen and coworkers proposed “a concept of
atelectasis” as a cause of impaired oxygenation during anesthesia [9]. However,
atelectasis could not be shown on conventional chest X-ray. With the
introduction of radiological computed tomography (CT), densities were seen in
dependent lung regions in anesthetized pediatric and adult patients [10, 11].
Morphological studies in various animals showed them to be atelectasis (see an
example in Fig. 1.1, left panel).
Atelectasis appears in around 90 % of all patients who are anesthetized
during spontaneous as well as mechanical ventilation and whether intravenous or
inhalational anesthetics are used [11]. The atelectatic area on a CT near the
diaphragm is on average 3–4 % of the total lung area but can easily exceed 15–
20 %. The amount of tissue that is collapsed is even larger, the atelectatic area
comprising mainly lung tissue, whereas the aerated lung consists of tissue and
air. Thus, 10–20 % of the lung is regularly collapsed at the base of the lung
during uneventful anesthesia before any surgery has been done. Abdominal
surgery does not add much to the atelectasis, but the lung collapse can remain for
several days in the postoperative period [12]. After thoracic surgery and
cardiopulmonary bypass, more than 50 % of the lung can be collapsed still
several hours after surgery [13]. The amount of atelectasis decreases toward the
apex that is mostly spared (fully aerated). It is likely that the atelectasis is a locus
of infection and that it can contribute to pulmonary complications [14, 15].
1.4 Prevention of Atelectasis

The major cause of atelectasis during anesthesia is closure of airways. This is
important to remember when considering techniques to prevent atelectasis or
reopen collapsed lung tissue. Compression of the lung might be suspected to be a
major or additional cause of atelectasis, but this is not likely. Airways will close
before alveoli collapse when the lung shrinks. This brings us to the second factor
that is needed to cause atelectasis, resorption of the gas that is trapped behind
closed airways. The higher the oxygen concentration, the faster is the resorption
of gas and atelectasis formation [11] (one may even ask how much of lung
collapse in the ARDS patient is caused by compression and how much by gas
resorption). Thus, fall in FRC and high oxygen concentration are both needed to
produce alveolar collapse, at least when considering the relatively short time of
most anesthesias.
Positive end-expiratory pressure

PEEP is a simple technique to increase lung volume and airway dimensions.
Depending on the magnitude of PEEP, airways may be reopened, but whether
the same level of PEEP is high enough to recruit collapsed alveoli is less certain.
Airways may close at an airway pressure of 6 cmH2O in a normal-weight
anesthetized subject [16] and, most likely, at higher pressure in an obese subject.
Perhaps a rule of thumb (not clearly tested) would be PEEP of 7 cmH2O when
BMI is below 25 kg/m2, 9 cmH2O up to 32 kg/m2, and higher in more obese
subjects to keep airways open. If this PEEP is applied before any atelectasis has
been produced, it is likely that it can prevent formation of it. To confuse things,
it should be mentioned that the application of 10 cmH2O PEEP consistently
reopens collapsed lung tissue. It requires some time, still only minutes, and may
rather be an effect of increased inspiratory airway pressure than of PEEP per se
[11]. It may not reopen all previously collapsed lung tissue, even if applied
during a prolonged period of time. Moreover, arterial oxygenation is not
improved in proportion to the decrease in atelectasis because of shift of blood
flow to more dependent, still atelectatic lung regions (Fig. 1.2). Also, PEEP
higher than 10 cmH2O may be associated with derangement in hemodynamics
[3]. This does not preclude the use of PEEP, but presumably an optimal and
individual PEEP is needed to balance the effects of recruitment and circulatory
impairment.
Fig. 1.2 Gamma camera images of lung blood flow in an anesthetized and mechanically ventilated patient
in the lateral position. The left panel shows more perfusion to the lower lung, the middle panel shows how
perfusion is almost absent in the upper lung with a general PEEP of 10 cmH2O, and the right panel shows
how perfusion is redistributed to the upper lung when a PEEP of 10 cmH20 has been applied to the
dependent lung only. The lung per se cannot be seen but the upper lung is larger than the lower one with no
or global PEEP (From Ref. [28], with permission by the publisher)
Recruitment maneuver:
A “sigh,” or a double tidal volume, has been suggested to reopen collapsed lung
and to improve gas exchange, both for intubated and non-intubated patients [17].
However, the amount of atelectasis does not change during normal tidal
breathing or by a “sigh” using an airway pressure of up to 20 cmH2O [11]. At a
sustained inflation of the lungs to an airway pressure of 30 cmH2O, atelectasis
decreases to approximately half the initial size. Additional inflations of the lung
to the same airway pressure (30 cmH2O) only result in minor further opening of
lung tissue after the first maneuver. To reopen all collapsed lung tissue in
anesthetized adults with healthy lungs, an airway pressure (recruitment pressure)
of 40 cmH2O is required. In morbidly obese patients with increased chest wall
elastance, a higher airway pressure is required to reach the same transpulmonary
pressure as in normal-weight subjects. A high airway pressure of 55 cmH2O,
kept for 10 s, was also used for lung recruitment in morbidly obese (BMI >45
kg/m2), anesthetized patient [18].
Recruitment maneuvers also have been used during cardiac surgery [19] (see
also below) and in the intensive care setting [20]. As there is a complex
interaction between time and pressure, the time frame possibly differs if other
recruitment pressures are used [21]. As an alternative, a stepwise increase in
PEEP can be used [22].
Oxygen and atelectasis during induction of anesthesia

Preoxygenation is provided to prevent hypoxemia in the event of a difficult
intubation of the airway and will for the anesthetist be an important procedure to
ensure maximum safety. However, the formation of atelectasis should be
recalled, and it will by itself shorten the “apnea tolerance time,” i.e., the time
before hypoxemia develops.
Avoiding the preoxygenation procedure and ventilating with 30 % instead of 100

% O2 prevents formation of atelectasis during the induction and subsequent
anesthesia [23]. In studies atelectasis appeared in all patients who were
preoxygenated with 100 % O2, was much smaller with 80 % O2, and was almost
absent with 60 % O2. However, the smaller amount of atelectasis with lower
oxygen concentration during induction remains only for a limited time. The
patients receiving 80 % O2 during induction had as much atelectasis as those on
100 % O2 40 min later [24]. This is because the gas trapped behind closed
airways consists of 80 % O2 and will be resorbed during the ensuing period and
finally results in airlessness, i.e., atelectasis. Reopening of closed airways by a
recruitment maneuver with lower O2 concentration, e.g., 40 %, even in the
absence of atelectasis, will replenish the closed region with lower O2 gas, and
this will slow down resorption atelectasis even more, hopefully for the rest of the
anesthesia.
Anesthesia might be induced during ventilation with CPAP that will prevent
the fall in FRC and atelectasis formation [25]. Oxygen can be used to full extent,
and, moreover, the lung volume is higher compared to no use of CPAP/PEEP,
resulting in a larger oxygen reservoir and increased safety time in the event of a
complicated intubation of the airway.
Oxygen and atelectasis during anesthesia

Ventilation of the lungs with pure oxygen after a vital capacity maneuver that
had reopened previously collapsed lung tissue resulted in a rapid reappearance of
the atelectasis [11]. If, on the other hand, 40 % O2 in nitrogen was used for
ventilation of the lungs, atelectasis reappeared slowly, and 40 min after the vital
capacity maneuver, only 20 % of the initial atelectasis had reappeared. Thus,
ventilation during anesthesia should be done with a moderate fraction of inspired
oxygen to prevent atelectasis formation, but if higher oxygen is considered
necessary, it can be given during PEEP ventilation.
Oxygen and atelectasis during emergence from anesthesia

Another situation where a high oxygen concentration is used is at the end of the
anesthesia. A post-oxygenation maneuver is regularly performed to reduce the
risk of hypoxemia during the wake up. This may be done in combination with
airway suctioning to eliminate secretions. However, the combination of
oxygenation and airway suctioning will most likely cause atelectasis, and there is
indeed no other potential maneuver that can compete with post-oxygenation and
airway suctioning in doing so.
The findings of atelectasis during anesthesia and the possibility to recruit lung
tissue with an inflation of the lung has prompted studies on the use of
recruitment maneuver at the end of the surgery and anesthesia. Again, the
influence of inspired oxygen plays an important role. Thus, recruitment at the
end of the anesthesia followed by ventilation with 100 % oxygen (the latter
again being common in routine anesthesia) caused new atelectasis within the 10
min period before anesthesia was terminated but not if ventilation was with
lower FiO2 [26]. Another approach to prevent atelectasis to persist into the
postoperative period is to use PEEP until extubation of the airway and to
continue with the CPAP for a limited time, e.g., 15–30 min during which period
inspired oxygen concentration is lowered to 30 % in the air. In a small study
where this technique was applied, atelectasis was reduced to less than a third
compared to control patients with no PEEP/CPAP as assessed by CT one hour
after wake up [27].
1.5 Individual Lung Ventilation

An individual lung ventilation technique was developed more than 30 years ago
in order to optimize ventilation distribution in proportion to individual lung
blood flow. It was successful in improving oxygenation but was considered too
complicated to be used in intensive care. Thus, it required that:
1. The patient was in the lateral position

2. A double lumen endobronchial catheter was inserted
3. Two ventilators were used

This made it possible to apply a higher PEEP to the lower lung where most
of the atelectasis should be and to ventilate each lung separately so that 50 % of
ventilation was given to the upper, nondependent lung and 50 % to the lower,
dependent lung. This was assumed to match the distribution of blood flow
between the two lungs [28] (Fig. 1.2). Despite its technical complexity, it was
also tested in anesthetized patients. Also, during anesthesia, gas exchange could
be improved, and CT scanning showed that atelectasis could efficiently be
removed from the dependent lung without undue overexpansion of the
nondependent lung. The concept has been revived recently, at least
experimentally, using better monitoring technique and, more importantly,
distributing ventilation in proportion to the lung mechanics of each lung rather
than its perfusion. This may not optimize gas exchange but should reduce stress
and strain of the lung with possible protective effect on inflammation. Having
this as the objective, ventilation will be distributed automatically between the
two lungs in proportion to their regional compliances (or, rather, their time
constants). Recruitment of collapsed lung tissue with no overexpansion and
ventilation of each lung at their optimum PEEP levels can be achieved, as shown
in an animal model [29] (see also Fig. 1.3). A simple pneumatic system that
allows the use of only one ventilator, still providing different PEEP to the two
lungs, does exist [30], and there is today a double lumen tracheal tube that
facilitates the insertion and fixation of the tube. The potential value of this in
thoracic surgery and in intensive care remains to be studied.
Fig. 1.3 Amount of atelectasis in the nondependent and dependent lung in piglets in the lateral position
after creating a ventilator-induced lung injury (repeated lung lavages and vulnerable ventilation). Note that
when the end-expiratory pressure decreased from 20 cmH2O to downward, atelectasis rapidly increased
from 12 cmH2O in the lower dependent lung and not until 6 cmH2O in the upper nondependent lung (From
Ref. [29])
1.6 One-Lung Ventilation

During one-lung ventilation (OLV), one lung is separated from ventilation to
enable surgery on that lung, and it does not participate in the pulmonary gas
exchange. There is a persisting perfusion that causes shunt and decreased arterial
oxygenation. Hypoxic vasoconstriction (HPV) reduces this blood flow, whereas
kinking of pulmonary vessels because of compression and distortion of the lung
seems to have less effect on blood flow [31].
The other lung is ventilated and perfused. The patient is normally in the
lateral position with the non-ventilated lung in the upper position to facilitate
surgery and the ventilated lung in the dependent position. Atelectasis is produced
in the dependent lung, and pulmonary shunt is regularly larger than 11 % and the
PaO2 reduced by 50 % or more during OLV [32]. A traditional approach to
mechanical ventilation during OLV has been high tidal volume (10–12 ml/kg)
and zero PEEP to the dependent ventilated lung, high tidal volume to keep the
lung open, and no PEEP to preserve the effect of the HPV in the nondependent
lung and minimize blood flow to it [33]. However, pulmonary complications are
common, both during the anesthesia per se with shunt and hypoxemia (see
above) and postoperatively. Pathophysiological disturbances include high airway
pressures, ventilation/perfusion mismatch with shunt, increased pulmonary
capillary pressure, and cyclic alveolar collapse. These events may result in
alveolar damage followed by pulmonary edema with diffuse alveolar injury,
leucocyte sequestration, and alveolar cytokine release, a series of events
frequently called mechanotransduction (for a review, see [34]). Moreover, on
termination of OLV there can be persisting hyperperfusion in the dependent,
ventilated lung, associated with an increased diffuse alveolar damage score, as
seen in porcine experiments [35].
Decrease of tidal volume (VT) to 5 ml/kg appears favorable in patients
undergoing thoracotomy [36] and, interestingly, reduces cyclic recruitment/de-
recruitment of atelectasis and poorly aerated tissue from 65 to 42 % in a porcine
model of OLV [37] (Fig. 1.4). This may possibly prevent or reduce an
inflammatory reaction. Moreover, the driving pressure , i.e., the difference
between end-inspiratory and end-expiratory airway pressure, seems to be an
important predictor of outcome in intensive care [38]. It is possible that OLV is
another condition where the driving pressure is particularly important.
Fig. 1.4 CT images of pig lungs during OLV with VT = 5 ml/kg or VT = 10 ml/kg in the left lateral
position. The left lung has been inscribed. Note the larger amount of atelectasis at end expiration and
slightly smaller amount at end inspiration with VT 10 compared to VT 5 ml/kg, thus resulting in larger
recruitment/de-recruitment with the large VT (From Ref. [35], with permission by the publisher)
As with conventional two-lung ventilation, there is no generally accepted

standard in determining an optimal level of positive end-expiratory pressure
(PEEP) during OLV. One option is to titrate PEEP aiming at best respiratory
compliance [39]. However, PEEP has potentially two opposing effects during
OLV. On the one hand, it may help to recruit and stabilize collapsed lung units in
the ventilated lung, reducing shunt in this lung. On the other hand, PEEP may
divert blood flow away from the ventilated lung to the non-ventilated lung,
thereby increasing shunt in that lung.
A recruitment maneuver has also been suggested to re-expand collapsed lung
during OLV [40]. In addition to an improved oxygenation, due to a reduction in
pulmonary shunt, such maneuver may contribute to a more even distribution of
ventilation, as suggested by a flattening of the CO2 curve during a tidal
expiration. Using CO2 washout may also enable detection of excessive airway
and alveolar dead spaces and guide in modifying VT and PEEP in OLV [41].
Pressure-controlled ventilation has been suggested to improve gas exchange
during OLV, as compared to volume-controlled ventilation. Still, this was not
confirmed in a study on patients undergoing thoracic surgery [42]. Indeed, if
ventilation was adjusted to reach the same tidal volume, there was no difference
in arterial oxygenation, neither was there a difference in end-inspiratory
(plateau) airway pressure. The only difference between the two modes was a
higher peak pressure in volume-controlled mode, which can be explained by the
difference in flow pattern of inspiratory gas between the two modes.
Another line for control of impaired gas exchange during one-lung
anesthesia is pharmacological interference with pulmonary blood flow [43].
Inhaled vasodilators such as nitric oxide (NO) and prostaglandins are considered
to have a local effect and divert blood away from non-ventilated to well-
ventilated lung regions. Interaction with the endothelin system appears to
enhance the redistribution of blood flow, as recently demonstrated [44].
Intravenous almitrine has been shown to increase pulmonary artery pressure in a
dose-dependent manner and to increase oxygenation in patients with acute
respiratory distress syndrome (ARDS) or with sepsis [45]. The effect has been
attributed to enhanced HPV and thus a reduction of blood flow in non-ventilated
lung regions. Finally, positioning of the patient can alter the degree of shunting
[46].
Virtually all anesthetics attenuate HPV [47], but the effect is small as is the
difference between anesthetics, e.g., between desflurane and isoflurane during
OLV [48]. Intravenous anesthetics blunt HPV even less, but they may trigger
inflammatory reactions more than inhaled drugs. Thus, in a study on patients
undergoing thoracic surgery during OLV (VT, 7 ml/kg), the effect on
inflammatory responses during propofol, desflurane, and sevoflurane anesthesias
were compared [49]. The major findings were that OLV increases the
concentrations of pro-inflammatory mediators in the ventilated lung and that the
inhalational anesthetics, but not propofol, decrease the alveolar inflammatory
response.
A special condition of OLV is its execution together with capnothorax, i.e.,
carbon dioxide insufflation into the pleural cavity. One indication for
OLV/capnothorax is atrial fibrillation surgery. This can be a rather challenging
situation with need of rapid decisions regarding ventilatory and circulatory
support. In an experimental model using electric impedance tomography (EIT),
OLV of the left lung together with right-sided capnothorax caused a decrease in
cardiac output, arterial oxygenation, and also mixed venous saturation, whereas
changes were less marked in OLV of the right lung and left-sided capnothorax.
The model might be useful for further studies [50].
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DOI 10.1007/978-3-319-19908-5_2
2. Where Should I Send My Patient After

the Operation?
Lukas Kreienbühl1, Tiziano Cassina1 and Marc Licker1
(1) Division of Anesthesiology, University Hospitals of Geneva, Geneva,
Switzerland

Marc Licker
Email: Marc-Joseph.Licker@hcuge.ch
2.1 Introduction
Thoracic surgery is associated with postoperative mortality rates ranging
between 2 and 5 % and cardiopulmonary complications varying between 20 and
40 %, resulting in prolonged hospital stay and increased healthcare costs [1].
Traditionally, a large proportion of thoracic surgical patients were admitted to
ICU. In light of growing health costs and budgetary constraints, patients are
increasingly admitted in HDU and PACU. In this chapter, we will address the
rationale of postoperative care management and selection criteria, guiding the
choice to admit the patient in ICU, HDU, or PACU, taking into account available
hospital resources, in addition to patient- and procedure-related factors (Fig.
2.1).
Fig. 2.1 Postoperative patient triage. Abbreviations: PACU postanesthesia care unit, HDU high
dependency unit, ICU intensive care unit
A clinician’s judgment on postoperative triage is largely based on predicting

the occurrence of “avoidable” major complications following surgery. The
overall risk profile can be approximated by combining patient- and procedure-
related risks. Based on large cohort analysis, several risk scoring systems,
including surgical and patient’s risk factors, have been developed and validated
to estimate postoperative morbidity and mortality in major noncardiac surgery
and also more specifically in thoracic surgery.
2.2 Risk Stratification

2.2.1 Patient-Related Risk Factors
2.2.1.1 General Risk Scores
The American Society of Anesthesiologists’ (ASA) classification of physical
health (from I to V) is universally applied for assessing preoperative health of
patients requiring any surgical, therapeutic, or diagnostic procedure. Although
ASA > II is associated with increased risk of postoperative morbidity and
mortality, large interobserver variability and poor specificity preclude accurate
estimation for individual patient risk [2].
The Charlson Comorbidity Index (CCI), composed of 19 weighted medical
diagnoses, is a valid predictor of 1-year mortality in medical patient population,
score greater than 5 being associated with 1-year mortality greater than 50 % [3].
In patients undergoing noncardiac surgery, CCI score ≥ 3 was associated with a
16-fold increase of death at one year [4]. Likewise, among lung cancer patients
undergoing curative resection, a CCI score ≥3 was associated with a tenfold
greater incidence of major complications [5].
The National Surgical Quality Improvement Program (NSQIP) was jointly
established by the American College of Surgeons (ACS) and the Department of
Veterans Affairs (VA) to compare risk-adjusted 30-day mortality between
different VA hospitals [6]. Based on 21 variables, the NSQIP is currently
available with web-based surgical risk calculator. Derived from the NSQIP
database, the Surgical Mortality Probability Model (S-MPM) includes three
relevant components – the ASA physical status, surgical risk class, and
emergency status – to predict all-cause postoperative mortality at 30 days [7]
(Table 2.1).
Table 2.1 Surgical Mortality Probability Model (S-MPM)
More specific for thoracic surgery, the Cardiopulmonary Risk Index (CPRI)
was developed in 1993 and consists in a combination of a cardiac risk index
(congestive heart failure, myocardial infarction during the previous 6 months,
greater than five premature ventricular contractions, arrhythmias, age >70 years,
important valvular aortic stenosis, poor general medical condition) and a
pulmonary risk index (BMI ≥27 kg/m2, smoking within 8 weeks of surgery,
productive cough within 5 days of surgery, diffuse wheezing or rhonchi within 5
days of surgery, FEV1/FVC <70 %, PaCO2 >45 mmHg). Later on, Ferguson et
al. have validated a simple scoring system (EVAD) that utilizes pulmonary
function test data (forced expiratory volume in one second [FEV1], diffusion
capacity of the lung for carbon monoxide [DLCO]) and patient age to predict the
likelihood of complications after major lung resection [8].
More recently, the Thoracoscore derived from the French national thoracic
database EPITHOR has incorporated eight independent risk factors (age, sex,
ASA physical status, performance status, dyspnea, priority of surgery, extent of
resection, carcinoma) to predict in-hospital mortality [9].
2.2.1.2 Cardiovascular Risk Scores

The Revised Cardiac Risk Index (RCRI) was developed for prediction of major
cardiac complications in non-emergent, noncardiac surgery [10] (Table 2.2).
Major cardiac complications include myocardial infarction, pulmonary edema,
ventricular fibrillation or primary cardiac arrest, and complete heart block. The
RCRI is composed of six variables of approximately equal prognostic
importance: high-risk surgery (including intrathoracic surgery), history of
ischemic heart disease, history of congestive cardiac failure, history of
cerebrovascular disease, insulin therapy for diabetes, and preoperative serum
creatinine >177 μmol/L. A RCRI ≥3 is associated with a risk of major
postoperative cardiac complications for more than 11 % of patients and may be
considered as a cutoff to delineate high-risk patients. Derived from the original
RCRI, a thoracic risk score (ThRCRI) for lung resections was established [11]
(Table 2.3). The predictive power of both of these scores in patients undergoing
lung resections is controversial.
Table 2.2 Revised Cardiac Risk Index
Table 2.3 Thoracic Revised Cardiac Risk Index (ThRCRI)
The Myocardial Infarction and Cardiac Arrest (MICA) risk calculator [12]
was developed with the intent to improve predictive power for major cardiac
adverse events as compared to RCRI. The model was based on analysis of the
National Surgical Quality Improvement Program (NSQIP) database with more
than 200,000 patients. Five predictors of perioperative risk of MICA at 30 days
were identified: type of surgery, age, functional dependency, creatinine >133
umol/L, and ASA class. The MICA risk calculator resulted in a more accurate
cardiac risk prediction than RCRI, although no data is available specifically for
thoracic surgical patients. The MICA risk calculator is available on the web.
Postoperative pulmonary complications (PPCs) include respiratory failure,
reintubation within 48 h, weaning failure, pneumonia, atelectasis, bronchospasm,
exacerbation of chronic obstructive pulmonary disease (COPD), pneumothorax,
pleural effusion, and various forms of upper airway obstruction. They are a
major cause of postoperative morbidity and mortality, possibly accounting for a
higher mortality than cardiovascular complications.
2.2.1.3 Pulmonary Risk Scores

The ARISCAT study established a risk score for the development of PPCs in a
mixed cohort of surgical patients [13]. Seven independent risk factors emerged:
low preoperative SpO2, preoperative anemia, age, lung infection in the previous
month, duration of surgery >2 h, upper abdominal or intrathoracic surgery, and
emergent surgery (Table 2.4). Both the patient-related and the procedure-related
risk factors contributed roughly 50 % to total risk. The score was prospectively
and externally validated across many European countries, with a satisfactory
predictive power especially for Western European countries [14].
Table 2.4 ARISCAT score
2.2.1.4 Lung Function Tests
The degree of dyspnea is correlated with the risk of postoperative mortality [15].
Standardized symptom-limited stair climbing is a simple cost-effective test to
objectively determine cardiorespiratory reserve and may have superior predictive
ability than traditional spirometry values [1]. The test involves climbing three
flights of stairs without interruption, equivalent to 12 m ascent that corresponds
to metabolic equivalents (METs) greater than 4. The inability to climb more than
12 m warrants further lung functional testing. A patient able to climb at least 22
m (5–6 flights of stairs) has a low risk of postoperative complication, regardless
of lung function test results [16].
FEV1 is a reliable predictor of perioperative complications in thoracic
surgery for patients with FEV1 <70 % [17]. According to the guidelines of
European Respiratory Society (ERS) and the European Society of Thoracic
Surgery (ESTS) on fitness for lung resection in cancer patients, a predicted
postoperative (ppo)-FEV1 <30 % separates patients into normal and high-risk
groups. It should be remembered that the calculated ppo-FEV1 may
overestimate the actual FEV1 on the first postoperative day by about 30 % and
that measured FEV1 on postoperative day one may provide more accurate
prediction of cardiopulmonary risk [18–20]. On the other hand, patients with a
moderate to severe obstructive pulmonary syndrome may have improved
respiratory dynamics after lung resection [21]. The ppo-diffusion capacity of the
lung for carbon monoxide (DLCO) is another powerful predictor of
perioperative complications. According to the ERS/ESTS guidelines, a ppo-
DLCO <30 % delineates a high surgical risk [1].
Peak VO2 allows further refinement of perioperative risk prediction. Patients
with values of peak VO2 >20 mL/kg/min qualify for resection up to
pneumonectomy, whereas values <10 mL/kg/min indicate a high risk for any
type of lung resection [22]. A value of ppo-peak VO2 <10 ml/kg/min is
associated with a mortality rate exceeding 50 % [23].
2.2.1.5 Age and Frailty

Given age-related decline in organ function and impairment in physiological
reserve, aging is considered a major risk factor for perioperative morbidity and
mortality. Sarcopenia affects not only limb skeletal muscles but also respiratory
muscles and those controlling the upper airways. Accordingly, obstructive sleep
apnea and occult aspiration occur more frequently particularly in the context of
underlying neurological disorders (e.g., previous stroke, dementia, Parkinson
disease) [24]. The risk of postoperative hypoxia and hypercapnia is increased
because of altered chemosensitivity, respiratory muscle weakness, and increased
pulmonary shunting. Impaired thermogenesis favors the occurrence of wound
infection, bleeding, and cardiac ischemia events, resulting in prolonged
postoperative recovery [25]. The risk of postoperative cognitive disorder
(POCD) is increased, especially with benzodiazepine premedication [26].
Frailty is a composite measure of geriatric conditions. It includes measures
of cognition, strength, energy, nutrition, physical mobility, mobility, and mood.
Patient assessment for frailty may be a valuable aid in determination of
operability and planning of postoperative care. A multidimensional frailty score
was elaborated for prediction of 1-year postoperative mortality [27]. It represents
an adaptation of the comprehensive geriatric assessment (CGA) and comprises a
total of nine items, with a maximal score of 15. The authors used a cutoff of a
score of 5, to distinguish between a high and a low risk of postoperative
mortality (mortality >10 %). Although superior to the ASA score for prediction
of 1-year mortality, its computation is complicated and time-consuming and
must be performed by a medical consultant familiar with the score.
2.2.2 Procedure-Related Risk Factors (Table 2.5)
Table 2.5 Risk classification according to the type of thoracic surgical procedure
2.2.2.1 Lung Resections

The literature on the risk of thoracic surgery primarily focuses on lung
resections, particularly in the context of cancer surgery. Broadly, the more
extensive the lung resection, the higher is the risk of developing postoperative
complications.
The highest risk of postoperative morbidity and mortality is associated with
extended pneumonectomy [28]. A study based on the Society for Thoracic
Surgeons (STS) General Thoracic Surgery Database (GTSD) examined major
morbidity and mortality after pneumonectomy in 1267 patients. The risk factors
independently associated with major adverse outcomes were age >65 years,
congestive heart failure, FEV1 <60 %, underlying benign lung disease, and
extended pneumonectomy. Overall mortality was 5.6 % and the incidence of
major morbidity was 30.4 %. A study based on data of the French national
database for thoracic surgery (EPITHOR) on 4498 patients with lung cancer
reports an overall mortality of 7.8 % for pneumonectomy, with risk factors for
mortality identified as age >65 years, ASA physiologic status ≥3, underweight,
right-sided pneumonectomy, and extended pneumonectomy [29].
A large study based on the STS GTSD, with 18,800 lung cancer resections
performed at 111 participating centers revealed an overall perioperative mortality
of 2.2 %. Independent predictors of mortality were pneumonectomy,
bilobectomy, ASA rating, functional status, renal dysfunction, induction
chemoradiation therapy, steroids, age, urgent procedures, male gender, FEV1,
and body mass index [30]. According to an analysis based on data of the
American National Cancer Database (NCDB) on almost 120,000 patients, 30-
day mortality of lung resections for non-small cell lung carcinoma (NSCLC) was
3.4 % overall, with a mortality of 8.5 % for pneumonectomies, 4 % for extended
lobectomies and bilobectomies, and 2.6 % for lobectomies and bilobectomies.
Mortality for wedge resections was 4.2 % and slightly higher than for
lobectomies, which may be explained by a higher rate of tumor recurrences, and
a lower functional preoperative status, indicating a more conservative surgical
approach.
Overall, a right-sided lung resection carries a higher risk of complications
than a left-sided resection owing to greater propensity to bronchopleural fistula
formation, a greater increase in right ventricular afterload, and potential
alteration in cardiac sympatho-vagal balance [29, 31].
2.2.2.2 Other Thoracic Surgical Interventions

Thoracic surgical interventions, which require one-lung ventilation (OLV) and a
thoracotomy, can be considered high-risk procedures. Similar to lung resections,
they expose patients to the risk of cardiovascular complications as well as
atelectasis, pneumonia, and ventilator-induced lung injuries (VILI) leading to
acute lung injury (ALI) or acute respiratory distress syndrome (ARDS).
For patients undergoing esophagectomies, a nomogram has been developed
to predict the occurrence and severity of postoperative complications [32].
Independent risk factors are increasing age, a history of cerebrovascular accident
(CVA) or transient ischemic accident (TIA), a history of myocardial infarction, a
reduced forced expiratory volume in one second (FEV1), electrocardiographic
(ECG) changes, and extensive surgery. The nomogram was validated and proved
useful for risk prediction in high-volume hospitals [33].
Lung or pleural biopsies and simple bullectomy with or without pleurodesis
under video-assisted thoracic surgery (VATS) are usually short-lasting and minor
procedures that require short-term admission in a PACU for monitoring
anesthesia emergence, titration of analgesic intravenous regimen, and detection
of residual air leakage, lung re-expansion, and atelectasis. Mediastinoscopies can
generally be monitored in PACU, with special attention to the risk of occult
postoperative hemorrhage.
Uni- or bilateral lung volume reduction surgeries in patients with severe
emphysema are considered high-risk procedures given preexisting severe airflow
limitations and major impairments in gas exchange. These patients require
cautious titration of analgesics (preferably epidural or paravertebral block) and
are preferably admitted in ICU or HDU given the risk of life-threatening
deterioration in pulmonary function (e.g., bronchopleural fistula, opiate-induced
hypercapnic acidosis).
2.2.2.3 Additional Surgical Risk Factors

Little evidence supports the use of a muscle-sparing thoracotomy as opposed to a
posterolateral thoracotomy, but incision length may be proportionally related to
post-thoracotomy complications [34]. Given limited tissue trauma and
consequent reduced neuroendocrine and inflammatory responses, VATS is
associated with lower rates of overall perioperative mortality, morbidity (e.g.,
pneumonia and atrial arrhythmia), as well as length of stay [31]. In the absence
of other major risk factors for postoperative complications, patients with a VATS
lung resection do not require neuraxial analgesic techniques and are commonly
managed in PACU for vital monitoring and anesthesia emergence.
Operative mortality may be lower if board-certified thoracic surgeons
perform a minimal case load of procedures [35]. Differences in postoperative
mortality rates between hospitals may also be explained by a different quality of
postoperative patient management [36]. As a consequence, local experience
should be included in the process of postoperative patient triage.
Surgery performed on an emergent basis has repeatedly been associated with
worse postoperative outcomes. Various pre- and postoperative scores integrate
this factor into risk stratification.
Finally, the occurrence of major intraoperative complications may require a
higher level of postoperative monitoring and treatment, than initially planned.
Myocardial ischemia, hemodynamically significant arrhythmias, refractory
hypotension or hypoxemia, bronchial aspiration, and major bleeding are
considered major complications that justify admission in HDU or ICU (Table
2.6).
Table 2.6 Summary of risk factors, indicating a high risk of postoperative complications
Patient-related risk factors Procedure-related risk factors
ASA physical status ≥4 High-risk procedure (according to Table 2.5)
S-MPM ≥6 points Major intraoperative complicationa
RCRI ≥2 points Low level of operator and hospital expertise
ThRCRI >1.5 points Emergency operation
ARISCAT >45 points
Preoperative FEV1 <60 %
ppo-FEV1 <30 %
ppo-DLCO <30 %
Peak VO2 <12 ml/kg/min
Liver dysfunctionb
ASA American Society of Anesthesiologists, S-MPM Surgical Mortality

Probability Model, RCRI Revised Cardiac Risk Index, ThRCRI Thoracic
Revised Cardiac Risk Index, FEV1 forced expired volume in one second, DLCO
diffusion capacity of the lung for carbon monoxide, VO 2 oxygen consumption,
MELD Model for End-Stage Liver Disease
aRefractory hypotension and/or hypoxemia, myocardial ischemia, cardiac
arrhythmias requiring treatment, major hemorrhage, and bronchial aspiration
bAccording to [37–39]
2.2.2.4 Anesthetic Management

Improving patient outcome can be achieved by implementing perioperative risk-
minimizing strategies:
1. Titration of anesthetic agents based on monitoring brain activity

2. Adoption of lung protective ventilatory settings
3. Achievement of optimal oxygen transport to match metabolic demands
4. Control of normothermia and hemostasis

5. Efficient pain control
The type and quality of postoperative pain control influences postoperative
triage, since insufficiently controlled postoperative pain increases the risk of
postoperative cardiopulmonary complications and length of stay [40]. Thoracic
epidural analgesia is considered the gold standard for thoracic surgery pain
management. Compared to systemic analgesia, it is associated with a lower
incidence of postoperative pneumonia and shorter duration of mechanical
ventilation [41]. Thoracic paravertebral block (PVB), performed percutaneously
by the anesthesiologist or directly placed by the surgeon, may provide similar
analgesia, at lower risk of hypotension and urinary retention [42]. In some
institutions, refractory hypotension caused by the thoracic epidural pain
treatment mandates transfer to HDU or ICU. Over the last decades, the incidence
of PPCs and the additional benefit of epidural over systemic analgesia have
markedly decreased [41].
2.3 Postoperative Selection of Patients for ICU, HDU, or
PACU Admission
For most patients, postoperative triage can be determined and planned
preoperatively, based on knowledge of preoperative patient- and procedure-
related risk factors, although intraoperative complications may modify the initial
assessment. Several risk scores take into account intraoperative complications
and can be used at the end of the operation, although none were specifically
developed or validated for thoracic surgery.
2.3.1 Scores and Guidelines

The Surgical Apgar Score (SAS) includes three intraoperative parameters −
blood loss, lowest mean arterial pressure, and lowest heart rate – that have been
shown useful to predict postoperative major complications or 30-day mortality
following noncardiac surgery [43]. So far, thoracic surgical patients have not
been included in this exploratory population sample (Table 2.7). The SAS has
been successfully validated in single centers and in an international study across
eight hospitals of eight different countries [44]. For the purpose of postoperative
triage, an Apgar ≤6 may signal a high risk of postoperative complications and
prompt the clinician to transfer a patient to HDU or ICU.
Table 2.7 Surgical Apgar score
The Physiological and Operative Severity Score for the enUmeration of

Mortality and morbidity (POSSUM) was developed for audit purposes and is a
British equivalent of the NSIQP in the United States. It is based on 12
physiological and 6 operative parameters and allows prediction of in-hospital
mortality and morbidity. It proved useful for prediction of postoperative
complications in lung resection patients [45]. Subsequently, the POSSUM
equation was improved and named Portsmouth-POSSUM (P-POSSUM) [46].
Risk calculation can easily be performed with a web-based risk calculator.
Several ICU scores, such as the Acute Physiology and Chronic Health
Evaluation (APACHE) score, the Simplified Acute Physiology Score (SAPS),
and the Mortality Probability Model (MPM) may be used for the purpose of risk
prediction and stratification in critically ill patients. Nevertheless, they only have
limited power to predict individual patient risk and do not take account of
surgical parameters.
The American College of Critical Care Medicine (ACCM) has issued
guidelines regarding selection criteria of patients admitted to HDU [47] and ICU
[48]. Admission in HDU should be considered for “patients who, after major
surgery, are hemodynamically stable, but may require fluid resuscitation and
transfusion due to major fluid shifts” and “who require close nurse monitoring
during the first 24 h.” Admission in ICU is restricted for a minority of patients
requiring “hemodynamic monitoring/ventilatory support or extensive nursing
care.”
2.3.2 Local Specificities

The spectrum of postoperative units extends from the day care ward to the
surgical ward, to the PACU, to the HDU, and to the ICU. Every hospital has a
unique combination of postoperative units, staffing, expertise, and technical
equipment, which greatly influence postoperative triage decisions. Triage
guidelines must therefore be adjusted to those specificities and developed by a
local multidisciplinary team composed of surgeons, anesthetists, pneumologists,
and intensivists.
In some institutions, all postsurgical patients are first transferred to PACU
before being transferred either to the ward or to HDU. This has the advantage of
disposing of more clinical information at the time of the final triage, since the
first postoperative hours are a period of major physiological variations with the
potential appearance of early pathological processes.
A patient transfer to the ward entails a substantial decrease in the quality and
frequency of monitoring. The provision of a medical emergency team, composed
of anesthetists and/or intensivists, may be a way to attenuate the risk [49] and
may influence postoperative triage decisions.
The triage process is strongly influenced by the ad hoc availability of beds.
But in addition, it also depends on aspects such as location of a unit within the
hospital (e.g., proximity to imaging facilities and to the operation rooms),
administrative barriers, culture of collaboration between staffs, and a unit’s level
of expertise.
Conclusion
Postoperative preventive and therapeutic management has to be carefully
planned in order to limit postoperative morbidity and mortality. The optimal
postoperative patient destination depends on the combination of patient-
related and procedure-related risk factors and on local specificities. Up-to-
date anesthetic management contributes significantly to decrease
postoperative risk and to reduce the need for high-level postoperative
monitoring. The general trend of thoracic surgery postoperative care moves
away from ICU toward HDUs or well-staffed and well-equipped PACUs for
many high-risk patients.
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DOI 10.1007/978-3-319-19908-5_3
3. Does It Matter How I Ventilate the

Patient During the Operation?
Laszlo L. Szegedi1
(1) Universitair Ziekenhuis Brussel and Vrije Universiteit Brussel, Brussels,
Belgium

Laszlo L. Szegedi
Email: Laszlo.Szegedi@uzbrussel.be
3.1 Introduction
With better surgical techniques and better and safer anesthesia drugs,
monitoring, and training, there is possibility to schedule patients for operations
and one-lung ventilation with more and more comorbidities, while the planned
surgery is more and more complex. Although the number of operable patients for
lung cancer surgery remains limited, the number of patients presenting for
surgery requiring one-lung ventilation (OLV) is increasing, because of the
broader indications for this technique. From the classical “absolute and relative”
indications for OLV, we moved to rather indications for facilitating surgery (the
majority of the indications for OLV), preventing cross-contamination of the
contralateral lung and controlling the distribution of ventilation to one lung.
These last years, the use of OLV increased not only for lung cancer surgery but
also for other newer surgical procedures or diagnostic procedures, like pleura
surgery, thoracic aorta surgery, esophagus surgery, thoracic spine surgery,
thoracic sympathicolysis, minimally invasive cardiac surgery, cardiac
electrophysiological surgery, whole-lung lavage, radiofrequency ablation of
hepatic tumors, and so on, without forgetting the increased number of lung
transplant procedures.
In the previous decades, because of its complexity, OLV was managed
almost exclusively by specialists in academic settings. Nowadays there is
increased necessity for all anesthesia staff members to master OLV techniques
and trying to obtain the best postoperative outcome for the patients.
Studies on how to one-lung ventilate the patients correctly are lacking, and
most of the recommendations for OLV are derived from two-lung ventilation
(TLV). Unfortunately, for the OLV addicts, most of the published studies were
done in intensive care unit (ICU) settings, during TLV of patients with either
acute respiratory distress syndrome (ARDS) or acute lung injury (ALI), and just
a few studied TLV during general anesthesia (GA) and even less OLV.
Khuri et al. [1] identified some of the determinants of 30-day postoperative
mortality and long-term survival after major surgery. While patient-dependent
risk and surgical factors are difficult to control by the anesthesiologists, the
anesthesia-dependent factors are under our responsibility – the type of
anesthesia, the pain management, the amount of administered fluids, and last,
but surely not least, the ventilatory management of the operated patients.
Postoperative pulmonary complications are the main cause of overall
perioperative morbidity and mortality in patients following GA. The incidence
of postoperative pulmonary complications may vary dramatically, ranging from
2 to 40 %, depending on the clinical treatment setting, the kind of surgery
studied, and the definition of postoperative pulmonary complications used [2].
The above mentioned facts are not really new, but they still remain a
common clinical problem. One should not forget that mechanical ventilation,
even if done in the best manner, is not a physiological process, because of
positive pressure, shear stress of the lungs, secretion of inflammatory mediators,
the gas mixtures used to ventilate, and the drugs and anesthetic gases which are
also potential independent variables in producing variable degrees of injuries to
the lung tissues.
3.2 The Protective Ventilation Was Born with ARDS

It’s worth to go back in history and see the evolution of proposed ventilator
strategies for anesthesia and mechanical ventilation. There are two interesting
studies, which should be mentioned here. More than 50 years ago, at the
beginning of modern mechanical ventilation, in 1963, Bendixen et al. found a
relation between the degree of ventilation and the magnitude of fall in arterial
oxygen tension [3]. Large tidal volumes (VTs) appeared to protect against falls
in oxygen tension, presumably by providing continuous hyperinflation, while
shallow VTs lead to atelectasis and increased shunting, with impaired
oxygenation. The second study [4], at the beginning of this century, a
multicenter, randomized study, compared two methods of mechanical ventilation
in patients with ALI and ARDS. Traditional ventilation method with VT of 12
ml/kg of predicted body weight (PBW) and an end-inspiratory airway pressure
(plateau pressure) of 50 cmH2O or less was compared with ventilation with an
initial VT of 6 ml/kg of PBW and a plateau pressure of 30 cmH2O or less. In
patients with ALI and ARDS, mechanical ventilation with a lower VT than was
traditionally used at that time resulted in decreased mortality and increased the
number of postoperative days without a need for mechanical ventilation.
Interesting to mention, too, is that the trial was stopped before the initially
proposed number of patients was reached, because the results were very
satisfactory.
Better understanding of the pathophysiology of ARDS has led to the
proposal that airway pressures and tidal volumes should be limited in ventilator
management of these patients [5]. This means that sometimes a rise in the
arterial partial pressure of carbon dioxide (PaCO2) should be accepted. Severe
hypercapnia and acidosis can have adverse effects, including increased
intracranial pressure, depressed myocardial contractility, pulmonary
hypertension, and depressed renal blood flow. The view that these risks are
preferable to the higher plateau pressure required to achieve normocapnia has
represented a substantial shift in ventilatory management. Cyclic inflation-
deflation of injured lung units or alveoli can exacerbate lung injury, and medium
to high levels of positive end-expiration pressure (PEEP) should be used to keep
alveoli open throughout the ventilatory cycle. Overall, this type of approach has
been termed lung-protective ventilation strategy. Ventilation with lower VT was
also associated with lower levels of systemic inflammatory mediators [6].
3.3 Is There a Rationale to Use Lung-Protective

Ventilation in Patients with Normal Lungs?
In a retrospective cohort study of patients with normal lungs at the onset of
mechanical ventilation in ICU, three different VTs were used for mechanical
ventilation (either <9, 9–12, or >12 ml/kg PBW). The study showed the
occurrence of ventilator-associated lung injury in these patients; however, their
incidence was significantly lower in those who were ventilated with lower VT
[7].
A preventive, randomized controlled trial, also in ICU settings, compared 6
vs 10 ml/kg PBW VTs in mechanically ventilated patients without ALI at the
start of mechanical ventilation. The percentage of occurrence of ALI/ARDS in
the group ventilated with 6 ml/kg was 2.6 % as compared to 13.5 % in the
second group [8].
These presented studies have identified the use of large VTs as a major risk
factor for development of lung injury in mechanically ventilated patients without
acute lung injury.
3.4 What About Patients Ventilated During General

Anesthesia?
A multicenter observational study of intraoperative ventilatory management
during GA and TLV showed that according to ideal body weight, approximately
30 % of patients are still ventilated with VTs higher than 10 ml/kg [9].
A recent meta-analysis [10] assessed whether incidence, morbidity, and in-
hospital mortality associated with postoperative lung injury are affected by type
of surgery and whether outcomes are dependent on type of ventilation. The total
incidence of postoperative lung injury was similar for abdominal and thoracic
surgery. Patients who developed postoperative lung injury were older, with
higher ASA scores and prevalence of sepsis or pneumonia, more frequently
received blood transfusions during surgery, and were ventilated with higher tidal
volumes, lower PEEP, or both, than patients who did not. ICU and hospital stay
were longer, and in-hospital mortality was higher in the patients with lung injury
than in those without injury and also higher in the patients who underwent
thoracic interventions as compared to abdominal surgery. Lung-protective
ventilatory strategies reduced the incidence of postoperative lung injury but did
not improve mortality.
The main differences between mechanical ventilation in ICU patients and
patients in OR settings are the duration of ventilation (short term, rarely
exceeding 6–8 h in OR, with in most cases an easy weaning, while in ICU
ventilation is most of times lasting for more than 24 h, with sometimes difficult
weaning). However, even short-term ventilation can produce lung damage, and
injurious mechanical ventilation may lead to epithelial cell apoptosis (far from
the lungs, including kidneys and the small intestine) [11].
As anesthesiologists and physicians first of all, we are striving to improve
quality of care in medicine and of course in mechanical ventilation too. There is
enough evidence in the literature with physiological rationale, meta-analyses, or
just small studies which suggest the low-VT option as a valuable one.
3.5 The Role of PEEP
The main determinants of ventilator-induced lung injury were proposed to be the
end-inspiratory transpulmonary pressure and the regional overdistension –
mainly determined by the high VT – which would not occur during “normal”
spontaneous breathing. There are other causes which even during very short-
term mechanical ventilation may cause injury to the lungs, surfactant
deactivation by mechanical ventilation causing problems in surfactant adsorption
and desorption, or elevated tissue stress between lung structures with different
mechanical properties. The second main mechanism is the low end-expiratory
lung volume injury, in other words the atelectasis-induced lung injury, the so-
called silent killer of peripheral airways [12].
Normally, in a healthy, erect subject, ventilation occurs above closing
capacity (CC) (the resting volume in the lungs at which peripheral airway
closure occurs, with inhomogeneity of distribution of ventilation and impaired
gas exchange and consequent risk of peripheral airway injury). Airway closure,
which can occur when the CC exceeds the end-expiratory lung volume (FRC), is
commonly observed in diseases characterized by increased CC (e.g., chronic
obstructive pulmonary disease, asthma, aging) and/or decreased FRC (e.g.,
obesity, chronic heart failure). Airway closure is a commonly observed
phenomenon during GA and not only in obese patients, where FRC is already
decreased.
Applying high VT with high inspiratory pressures, during mechanical
ventilation, will lead to barotrauma or volutrauma, with release of inflammatory
cytokines interleukin (IL)-1 beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha
leading to biotrauma. On the other hand, if low VT is used without PEEP,
atelectrauma will occur with the same consequences [13].
Atelectasis and pulmonary gas exchange were studied in supine patients
without lung disease. Positive end-expiratory pressure reduced the atelectasis in
all patients but did not change the degree of shunt. It was concluded that the
development of atelectasis in dependent lung regions is a major cause of gas
exchange impairment during GA, during both spontaneous breathing and
mechanical ventilation, and that PEEP diminishes the atelectasis, but not
necessarily the shunt [14]. Even if a PEEP is associated with low-VT ventilation,
prolonged impaired lung function after major surgery is not ameliorated [15].
3.6 The Role of Oxygen

Some minutes after induction of general anesthesia, in healthy patients, FRC
decreases by almost 20 % [16]. All anesthetic drugs (but ketamine), even with
spontaneous breathing, decrease FRC after induction of anesthesia. During sleep,
FRC is reduced during rapid eye movement (REM) sleep at the same level as
after induction of GA. Reduced respiratory muscle tone and airway closure are
likely causative factors. However, during sleep, atelectasis does not develop,
because the FiO2 is low [17]. At the induction of GA, preoxygenation with FiO2
of 80 % instead of 100 % may be sufficient in most patients with no anticipated
difficulty in managing the airway, but time to hypoxemia during apnea
decreases. Continuous positive airway pressure (CPAP)/PEEP was proposed to
prevent fall in FRC. Inspired oxygen concentration of 30–40 %, or even less,
should suffice if the lung is kept open [18].
3.7 Alveolar Recruitment Maneuver

Alveolar recruitment maneuvers (ARMs) were proposed to ameliorate
oxygenation before applying a PEEP [19]. Different methods of ARM were
described. But very simply explained, it consists of inflation to an airway
pressure of 40 cmH2O for 10 s and to higher airway pressures in patients with
reduced abdominal compliance (obese and patients with abdominal disorders),
while respecting a driving pressure of maximum 15 cmH2O and increasing
PEEP. A low and constant driving pressure during all the procedure allows an
increased safety margin when a higher PEEP is employed during ARM. Alveolar
recruitment maneuvers followed by PEEP reduce atelectasis and improve
oxygenation in morbidly obese patients, whereas either PEEP or ARM alone
does not [20]. The effect of ARMs on patient outcome in the postoperative
period is, however, not yet known.
There is large evidence that during GA, lung-protective ventilation should be
used. Ideally it should be a combination of low VT (how low is low?) and ARM
(early and repeated) before applying PEEP. A study comparing standard
mechanical ventilation lasting more than 2 h (VT 9 ml/kg, without PEEP or
ARM) versus lung-protective ventilation (VT 7 ml/kg with PEEP 10 cmH2O and
ARM) obtained better inflammatory responses and better chest X-ray
postoperatively in the group with protective ventilation [21]. The IMPROVE
study (n = 400) [22] compared ventilation with VTs of 10–12 ml/kg, without
PEEP or ARM, to ventilation with VT of 8 ml/kg, with PEEP 6–8 cmH2O and
ARM after intubation and repeated every 30–40 min. As compared with a
practice of non-protective mechanical ventilation, the use of a lung-protective
ventilation strategy in intermediate-risk and high-risk patients undergoing major
abdominal surgery was associated with improved clinical outcomes.
The PROVHILO international study (n = 900) [23] compared two groups
during abdominal surgery too, using the same VT of 8 ml/kg for both groups, but
in the conventional ventilation group with a PEEP <2 cmH2O and in the
protective ventilation group with a PEEP of 12 cmH2O and ARM after
intubation, after any disconnection of ventilator, and before extubation.
Compared with patients in the lower PEEP group, those in the higher PEEP
group developed intraoperative hypotension and needed more vasoactive drugs.
The high level of PEEP and ARM during open abdominal surgery did not protect
against postoperative pulmonary complications. Their recommendations were
that an intraoperative protective ventilation strategy should include a low tidal
volume and low PEEP (not the 12 cmH2O used), without ARM.
After all these large, international studies, with different and sometimes
contradictory findings, the question, if they are of real help or more confusing,
may be justified [24].
3.8 Pressure- or Volume-Controlled Two-Lung

Ventilation
There are benefits for both of them; however, the incidence of perioperative
complications is not different. The best mode depends on the patient and the
anesthesiologists should apply the mode that they best know and master. Even in
obese patients, no real benefits could be demonstrated when using these two
types of mechanical ventilation, which remains rather physician dependent, than
really goal oriented.
Mechanical ventilation should no longer be considered only as a way to
supply gas exchange during GA. Inadequate ventilatory settings can produce
lung damage even in patients with healthy lungs, even for short periods of
mechanical ventilation, not only in ICU, but in OR too. Lung-protective
ventilation is the standard of care in most ARDS patients and it should become
in OR too.
The relative contribution of low VT, low pressures, and PEEP in prevention
of ventilator-induced lung injury is uncertain. Driving pressure (VT/compliance
of respiratory system (CRS)), in which VT is intrinsically normalized to
functional lung size (instead of predicted lung size in healthy persons), was
suggested to be a better parameter associated with survival than VT or PEEP in
patients who are not actively breathing [25].
3.9 The “Baby Lung” During OLV
The “baby lung” concept was described by Gattinoni et al., to characterize the
normally aerated lung tissue in ARDS/ALI patients, which was comparable to
the lung dimensions of a young child. They suggested that in these patients, the
CRS is linearly related to the dimensions of the aerated lung regions, which is
not at all stiff, but with normal elasticity; thus, for ventilator-induced lung injury,
what is important is the ratio of VT to aerated lung volume and to body weight;
the smaller the “baby lung,” the greater is the potential for unsafe mechanical
ventilation [26]. This principle may be extrapolated for OLV also.
3.10 One-Lung Ventilation with Lessons from Two-Lung

Ventilation?
One-lung ventilation is a technique that adds supplementary difficulties to the
complexity of anesthesia management per se (generally combined sometimes
with epidural technique) and to the management of patients which present in
most of cases with compromised pulmonary (and other organ system) functions.
During OLV, one lung is ventilated, while the other is excluded from
ventilation and remains perfused, adding an extra intrapulmonary shunting, to
the physiologic and general anesthesia-induced one. It is normal that at the start
of OLV, if keeping the same inspired oxygen concentration and the same
hemodynamic and metabolic status for the patient, the arterial oxygen partial
pressure will decrease, and the alveolar-to-arterial oxygen partial pressure
difference will increase. Fortunately, there are some mechanisms which to divert
blood flow from the non-ventilated lung toward the ventilated one, trying to
diminish shunt. These are active, like the hypoxic pulmonary vasoconstriction,
and passive, like gravitational redistribution of blood flow from the upper, non-
ventilated lung toward the lower, ventilated one, surgical manipulation of lung
tissue (this may be beneficial through mechanical manipulation; however, in the
same time, it may lead to secretion of vasodilatory and pro-inflammatory
mediators), preexisting lung pathology, and ventilatory methods. It is obvious
that in clinical situations it is impossible to determine the individual contribution
of each of these factors.
In the last few decades, there is a significant decrease of reported
intraoperative hypoxemia during OLV, from 20 to 25 % reported in the 1970s to
less than 5 % nowadays (some are saying even less).
This decrease is multifactorial: better surgical techniques, new anesthetic
drugs, better lung-separating devices, better training with hands-on workshops at
congresses, and the routine use of the fiber-optic bronchoscope for positioning of
lung-separating devices and better ventilatory techniques.
In the textbooks of thoracic anesthesia (unfortunately most of them available
are more than 10 years old!), the recommendations for ventilatory management
during thoracic surgery are as follows: maintain TLV until the pleura is opened;
manage OLV by increasing the FiO2 if necessary to 100 %; use VTs of 10–12
ml/kg; adjust respiratory rate in order to maintain normocapnia; even if an auto-
PEEP is present, try to eliminate it; and use total intravenous anesthesia instead
of inhaled anesthetics. If hypoxemia occurs, check the position of the double-
lumen tube, apply a CPAP to the nondependent lung, use low levels of PEEP to
the dependent lung, resume TLV, or ask the surgeon to clamp the pulmonary
artery for pneumectomy. These criteria, which are focusing almost only on
oxygenation, are relatively inadequate for modern OLV. A couple of years ago,
the author of this chapter has published a study on COPD patients during OLV,
in which high VT was used with variable respiratory rate and constant minute
volume, in order to diminish intrinsic PEEP. Fortunately, all the patients were
evaluated without postoperative complications, but such studies are nowadays,
for obvious reasons, no more possible [27].
Even with a decrease in the incidence of hypoxemia during OLV,
anesthesiologists are aware that not only hypoxemia is the problem during OLV,
but the possibility of lung injury too.
In an observational study including patients undergoing lung surgery, two
clinical forms of ALI were described: a delayed-onset form triggered by
intercurrent complications and an early form associated with preoperative
alcohol consumption, pneumectomy, high intraoperative pressures, and
excessive fluid intake over the first 24 h [28].
One-lung ventilation with VT as used during TLV is a suggested algorithm
but may impose mechanical stress of the dependent lung and potentially
aggravate alveolar mediator release. A study comparing ventilation with
different VTs assessed if there were changes in pulmonary immune function,
hemodynamics, and gas exchange. Patients undergoing open thoracic surgery
were randomized to receive either minute volume with a VT of either 10 ml/kg
or 5 ml/kg, and respiratory rate was adjusted to obtain normal PaCO2 during and
after OLV. Fiber-optic bronchoalveolar lavage (BAL) of the ventilated lung was
performed, and cells, protein, TNF-alpha, IL-8, soluble intercellular adhesion
molecule (sICAM)-1, IL-10, and elastase were determined in the BAL. In all
patients, an increase of pro-inflammatory variables was found. The time courses
of intra-alveolar cells, protein, albumin, IL-8, elastase, and IL-10 did not differ
between the groups after OLV and postoperatively. TNF-alpha and sICAM-1
concentrations were significantly smaller after OLV with the lower VTs. These
results indicate that OLV too may induce epithelial damage and a pro-
inflammatory response in the ventilated lung, just like TLV. Reduction of VT
during OLV may reduce alveolar concentrations of TNF-alpha and of sICAM-1
[29].
Most of clinical studies using BAL fluid analysis have demonstrated
pulmonary inflammatory reactions in the ventilated, dependent lung. However,
few clinical studies have investigated such inflammatory reactions in the
dependent lung compared with the collapsed nondependent lung. A study
comparing the inflammatory reactions in the dependent lung and the
nondependent lung during thoracic surgery was performed on patients during
OLV, under total intravenous anesthesia with propofol and remifentanil. Levels
of inflammatory mediators, TNF-alpha, IL-1 beta, IL-6, IL-8, IL-10, and IL-12,
were measured before and after OLV. All inflammatory mediators were elevated
at the end of surgery compared with their baseline levels; however IL-6 was
significantly higher in the dependent lung than in the nondependent lung [30].
One-lung ventilation can damage the ventilated lung just like TLV.
Nevertheless, using protective approach OLV to prevent lung injury, by
reduction of VT and application of PEEP, did not completely inhibit
thromboxane B2 formation in isolated rabbit lungs [10, 31] or the enhanced
alveolar pro-inflammatory response in laboratory animals.
During esophagus surgery, protective ventilatory strategy decreased the pro-
inflammatory systemic response, improved lung function, and resulted in earlier
extubation [32].
In a survey on the habitudes of thoracic anesthesiologists, done by the
thoracic subcommittee and endorsed by the European Association of
Cardiothoracic Anesthesiology (EACTA), the good news for the management of
OLV is that 100 % of the respondent anesthesiologists were using fiber-optic
bronchoscopy to position and check the position of lung-separating devices
during OLV, which is an enormous help to avoid hypoxemia due to malposition
of these devices. Concerning the modes of one-lung ventilation, 60 % of the
anesthesiologists were using volume-controlled modes, while 40 % pressure-
controlled modes for OLV. The inspiratory airway pressures used during PCV
ranged from 15 to 40, which may be considered as high. During VCV, the
acceptable plateau pressures varied from 15 to 35. There are studies
investigating the VCV vs. PCV during OLV. In one study [33], it was found that
oxygenation was better when using PCV as compared to VCV. Ten years later,
another study assessed the same modes and did not find any differences [34].
This difference in the outcome of the studies might be due to the patients
included in the studies: differences were found in favor of PCV for OLV of
patients with altered lung functions, the other study included only healthy lung
patients.
A study evaluated the use of ARM to decrease the VT used during OLV in
piglets. It was found that ARM improves aeration and respiratory mechanics.
Moreover, in contrast to OLV with high VT, OLV with reduced VT did not
reinforce tidal recruitment, indicating decreased mechanical stress [35]. Alveolar
recruitment maneuvers during OLV, applied to the ventilated lung, improve
oxygenation significantly, to PaO2 values comparable of those during TLV [36].
Unfortunately, there are no data on the effects of OLV on postoperative
ventilation/perfusion matching. An animal study in a pig model evaluated the
influence of OLV on ventilation /perfusion mismatch using a single-photon
emission computed tomography technique and related these findings to lung
histopathology after OLV. One-lung ventilation resulted in significant
ventilation/perfusion mismatch, hypoperfusion, and alveolar damage in the
dependent lung, contributing to gas exchange impairment after OLV [37].
Data suggest that pro-inflammatory reactions during OLV are influenced by
the type of general anesthesia. Several prospective, randomized studies suggest
an immunomodulatory role for the volatile anesthetic sevoflurane during OLV
for thoracic surgery with significant reduction of pro-inflammatory mediators
and a significantly better clinical outcome (defined by postoperative adverse
events), as compared to intravenous propofol [38].
When BAL was done in the nondependent lung too, less increase in
inflammatory mediators was found with sevoflurane as compared with propofol
anesthesia, which suggest decreased postoperative adverse events when using
sevoflurane. Better effects were found for desflurane too, as compared to
propofol anesthesia [39]. It seems that the old recommendations of using total
intravenous anesthesia for OLV had become obsolete by the introduction of new
halogenated agents. Volatile anesthetics inhibit the local alveolar, but not the
systemic inflammatory response [40].
Before, we tried to maintain normocapnia, but a recent study showed that
normocapnia is not mandatory for OLV. At the contrary, under intravenous
anesthesia, therapeutic hypercapnia inhibited local and systematic inflammation
and improved respiratory function after OLV in lobectomy patients without
severe complications [11].
Some surgeons advocate that a high fraction of inspired oxygen (FiO2) is
needed for wound healing. However, this theory remains controversial. Indeed a
higher arterial oxygen partial pressure (PaO2) is needed to force oxygen into
injured and healing tissues, particularly in the subcutaneous tissue, fascia,
tendon, and bone, the tissues most at risk for healing.
In order to use a lower FiO2, the effects of low VT with limited plateau
pressure to try to establish ideal ventilatory parameters were studied, using a
crossover design; however, just low VT combined with PEEP resulted in reduced
oxygenation [41].
In a healthy porcine lung model of OLV, moderate PEEP can improve
oxygenation. This effect implies both expiratory and inspiratory pulmonary
recruitment. Co-administration of inspired nitric oxide was ineffective [42].
Positive end-expiratory pressure is commonly applied to the ventilated lung
to try to improve oxygenation during OLV, but it is an unreliable therapy and
occasionally causes PaO2 to decrease further. The effects of PEEP on
oxygenation depend on the static compliance curve of the lung to which it is
applied. The effects of the application of 5 cmH2O PEEP on oxygenation during
OLV correspond to individual changes in the relation between the plateau end-
expiratory pressure and the inflection point of the static compliance curve. When
the application of PEEP causes the end-expiratory pressure to increase from a
low level toward the inflection point, oxygenation is likely to improve, but, if the
addition of PEEP causes an increased inflation of the ventilated lung that raises
the equilibrium end-expiratory pressure beyond the inflection point, oxygenation
is likely to deteriorate. Unfortunately, there is yet no possibility for the use of a
device that could establish the inflection point in the current clinical practice
[43].
Applying CPAP to the non-ventilated lung can have beneficial effects.
Results suggest that increased IL-1 or TNF-alpha production by alveolar
macrophages may be responsible for fever caused by atelectasis. By applying
CPAP to the non-ventilated, atelectatic lung, this may be prevented. In the same
time, it is beneficial for reducing FiO2 during OLV [44].
Re-expansion pulmonary edema is a rare complication caused by rapid re-
expansion of a collapsed lung. Elevated levels of pro-inflammatory cytokines in
pulmonary edema fluid are suggested to play important roles in its development.
Pro-inflammatory cytokines are upregulated upon re-expansion and ventilation
after short-period lung collapse, though no changes are observed in pulmonary
capillary permeability [45].
Because of the regular use of fiber-optic bronchoscope, the positioning of
lung-separating devices became safer; thus, very high FiO2 is most of times not
necessary. High FiO2 may induce atelectasis, and it was shown that during OLV
inflammatory and oxidative responses were more favorable when using lower
(under 50 %) FiO2 [46].
Conclusions
The practice of OLV practice has changed over the past few decades, with VT
decreasing significantly. However, patients during OLV are still ventilated with
large, and perhaps too large, VT. Even if there is increasing evidence for the use
of protective settings for OLV, however, what are the optimal settings?
According to the EACTA thoracic subcommission’s survey, still less than 60 %
of anesthesiologists who are regularly performing OLV are using higher VT than
6 ml/kg, less than 50 % are doing no ARM at all, just a few of the rest are doing
ARM before applying a PEEP, and just a very few use FiO2 less than 100 % for
induction of GA, and a lot 100 % for OLV. What is the low VT that we may use
during OLV to keep the balance between oxygen delivery and prevention of lung
injury, and how much is the optimal PEEP that we should use during OLV? The
ventilatory method for OLV (pressure vs volume controlled) seems to be not an
issue, given that the differences are not really relevant. As an alternative for
conventional ventilatory methods, high-frequency jet ventilation was proposed
too; however, studies are lacking. Unfortunately, even if it remains evidence
based, the use of ARM, low VT, low driving pressure, PEEP, and low FiO2 is not
yet generally accepted by thoracic anesthesiologists. Prospective studies to
evaluate optimal settings for OLV (while keeping the balance between
oxygenation and lung injury) are needed; the more and more sophisticated
monitoring devices that are available for clinical use, like electrical impedance
tomography or volumetric capnography, could help assess these uncertainties.
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DOI 10.1007/978-3-319-19908-5_4
4. Can Postoperative Pulmonary

Complications Be Objectively Evaluated?
Marcelo Gama de Abreu1 , Thomas Kiss1, Lluis Gallart2
and Jaume Canet2
(1) Department of Anesthesiology and Intensive Care Therapy, Pulmonary
(2) Department of Anesthesiology, Hospital Universitari Germans Trias i Pujol,

Marcelo Gama de Abreu
Email: mgabreau@uniklinikum-dresden.de
4.1 Introduction
It has been estimated that more than 230 million major surgical procedures are
conducted every year across the world and that more than 1 % of those
procedures, i.e., approximately 2.6 million, carry a high risk of complications
[1]. Again, roughly half of the patients who are submitted to high-risk
interventions experience complications, and more than 300,000 die during the
hospital stay. Among those complications, pulmonary adverse events, or
postoperative pulmonary complications (PPCs), occur as often as cardiac and
circulatory adverse events [2]. Observational studies have shown that PPCs
occur in up to 10 % of patients who undergo surgery under general anesthesia
[3]. In patients with low preoperative peripheral oxygen saturation, upper airway
infection up to 1 month before surgery, and anemia and in the elderly, the risk of
PPCs increases importantly. Also the type of surgery, emergency procedures, and
the duration of surgery itself are associated with a higher risk of developing
adverse pulmonary events [3]. Following upper abdominal and thoracic surgery,
the incidence of PPCs can be as high as 19–59 % [4].
There are different reasons for assessing the risk of PPCs. The stratification
of patients according to the likelihood of such complications allows preventive
measurements to be taken, such as planned admission in units better equipped
for monitoring and treating those patients, thereby decreasing the risk of further
complications that might develop. It has been shown that postoperative lung
failure dramatically increases the risk of death following abdominal and thoracic
surgery [5]. Furthermore, when groups of patients with a similar probability of
developing PPCs are identified, specific interventions to prevent them can be
designed and trials may be better planned. Last but not the least, allocation of
financial resources can be conducted in a more objective and efficient way, given
that such complications have marked economic impact on health systems.
In the present chapter, we will present the state of the art of the evaluation of
PPCs. We will critically review the most commonly used definitions of PPCs
and provide a thorough appraisal of the current tools for stratifying patients at
higher risk. We will present a comprehensive state of the art in prediction of
PPCs, focusing on patients undergoing thoracic surgery procedures, and the
particularities of this type of intervention.
4.2 Definitions of Postoperative Pulmonary

Complications
In clinical practice, any postoperative pulmonary adverse event can be seen as a
PPC, independent of the degree of severity or further consequences it may cause.
Among the most common events considered as PPC are [2, 6–8] (a) respiratory
failure from pulmonary or cardiac origin, (b) pneumonia and respiratory
infection, (c) pleural effusion and atelectasis, (d) pneumothorax, (e)
bronchospasm, and (f) need for noninvasive respiratory support or reintubation.
Although apparently less harmful, and occurring more frequently than other
events, peripheral oxygen desaturation requiring supplemental oxygen has been
considered also a PPC by different authors [9–12]. It is worth noting that once a
PPC occur, the average hospital stay is prolonged and the risk of in-hospital
death increases despite the subjectively attributable severity of the specific event
[3–13]. Obviously, the incidence of PPCs varies considerably depending on the
definition used, and this may impact on the interpretation of studies and use of
risk scores.
Recently, the joint task force of the European Society of Anaesthesiology
(ESA) and the European Society of Intensive Care Medicine (ESICM) on
perioperative outcome measures proposed specific definitions for PPCs based on
a consensus among experts and more common used terms across different
studies [12]:
Acute respiratory failure – Postoperative PaO2 <60 mmHg on room air, a
PaO2/FIO2 ratio <300 mmHg, or arterial oxyhemoglobin saturation
measured with pulse oximetry <90 % and requiring oxygen therapy.
Although not directly addressed by the ESA-ESICM task force [12],
respiratory failure may be subdivided into mild, moderate, and severe
forms. The mild form refers to adequate response to supplemental oxygen,
the moderate form corresponds to inadequate response to supplemental
oxygen requiring noninvasive or invasive mechanical ventilation, and the
severe form is the development of the acute respiratory distress syndrome
[14].
Atelectasis – Lung opacification with a shift of the mediastinum, hilum, or
hemidiaphragm toward the affected area and compensatory overinflation in
the adjacent non-atelectatic lung.
Respiratory infection – The patient has received antibiotics for a suspected
respiratory infection and met one or more of the following criteria: new or
changed sputum, new or changed lung opacities, fever, and white blood cell
count >12 × 109 L−1.
Pleural effusion – Chest radiograph demonstrating blunting of the
costophrenic angle, loss of sharp silhouette of the ipsilateral hemidiaphragm
in upright position, evidence of displacement of adjacent anatomical
structures, or (in supine position) a hazy opacity in one hemithorax with
preserved vascular shadows.
Pneumothorax – Air in the pleural space with no vascular bed surrounding
the visceral pleura.
Bronchospasm – Newly detected expiratory wheezing treated with
bronchodilators.
Aspiration pneumonitis – Acute lung injury after the inhalation of
regurgitated gastric contents.
Usually, these adverse events are grouped together to build a so-called
collapsed composite. When one component variable of the composite outcome is
fulfilled, the patient is considered to have a PPC. One of the major advantages of
using collapsed PPC composites is that they may increase the power of studies
addressing interventions. Since the incidence of a particular event can be
relatively low, accounting for a group of events that can be influenced by a
specific intervention seems reasonable. On the other hand, it has been suggested
that differences in the frequency of component variables of a collapsed
composite, as well as their severity, should be ideally comparable, or at least
their relative weighs taken into account [15].
4.3 Postoperative Pulmonary Complications After

Thoracic Surgery
One of the particularities of surgical interventions in the thorax, mainly those
involving lung procedures, is that one or more of the adverse events previously
mentioned represent an otherwise common consequence of surgery. For
example, partial atelectasis of the operated lung, pleural effusion, and ipsilateral
pneumothorax are more likely related to the surgical procedure and/or the
preoperative condition than to the intraoperative respiratory or circulatory
management. On the other hand, the presence of prolonged air leaks, acute lung
edema, pulmonary embolism, purulent pleuritis, and even hemorrhage [16] may
be partly related to the modulation of the immune, pro-inflammatory, and pro-
coagulatory responses, which are influenced, at least in part, by the management
of hemodynamics and ventilation during thoracic surgery.
Given that mild forms of acute respiratory failure likely represent the most
common adverse event following thoracic surgery, and aiming at delivering a
comprehensive, but also specific list of adverse pulmonary events that is
summarized in Table 4.1.
Table 4.1 Most frequent and relevant postoperative pulmonary complications after thoracic surgery
Adverse Definition Observation
pulmonary
event
Acute Postoperative PaO2 <60 mmHg on room air, a It may present as mild, moderate, or
respiratory PaO2/FIO2 ratio <300 mmHg, or arterial severe form
failure Mild, adequate response to
oxyhemoglobin saturation measured with pulse
oximetry <90 % and requiring oxygen therapy [12] supplemental oxygen; moderate,
inadequate response to supplemental
oxygen requiring noninvasive or
invasive mechanical ventilation;
severe, acute respiratory distress
syndrome [14]
Prolonged air Air leak requiring >7 days of postoperative chest After acute respiratory failure,
leak tube drainage [16] possibly the most common
pulmonary complication following
thoracic surgery
Respiratory Receiving antibiotics for a suspected respiratory
infection infection and met one or more of the following
criteria: new or changed sputum, new or changed
lung opacities, fever, white blood cell count >12 ×
109 L−1 [12]
Postoperative Bleeding through the chest tubes requiring
hemorrhage reoperation or three or more red blood cell packs
[16]
Atelectasis Lung opacification with a shift of the mediastinum,
hilum, or hemidiaphragm toward the affected area
and compensatory overinflation in the adjacent non-
atelectatic lung [12]
Pneumothorax Air in the pleural space with no vascular bed As far as not related to the surgical
surrounding the visceral pleura [12] procedure alone
Bronchospasm Newly detected expiratory wheezing treated with In mechanically ventilated patients,
bronchodilators [12] increased airway pressure during
positive-pressure ventilation or
prolonged expiratory phase [16]
Pulmonary As documented by pulmonary arteriogram or
embolism autopsy or supported by a ventilation/perfusion
radioisotope scans [16]
Aspiration Acute lung injury after the inhalation of regurgitated
pneumonitis gastric contents
Pleural Chest radiograph demonstrating blunting of the As far as not related explained by the
effusion costophrenic angle, loss of sharp silhouette of the preoperative patient condition alone
ipsilateral hemidiaphragm in upright position,
evidence of displacement of adjacent anatomical
structures, or (in supine position) a hazy opacity in
one hemithorax with preserved vascular shadows
Acute Evidence of fluid accumulation in the alveoli as Not explained by poor cardiac
pulmonary documented by lung imaging function
edema
Purulent Receiving antibiotics for a suspected infection As far as not related explained by the
pleuritis preoperative patient condition alone
4.4 Risk of Developing Postoperative Pulmonary

Complications
Along the last 16 years, more than 50 risk factors for PPCs have been identified
and discussed in the literature [9, 10, 17]. Factors related to development of
PPCs can be seen also as “predictors” and addressed in terms of relative
contribution to the odds of developing such complications. They may be
combined by means of statistical models into scores that will ultimately reflect
the probability of patients to develop PPCs.
The milestone of a structured presentation of factors related to the
development of pulmonary adverse events in surgery patients has been
established by the American College of Physicians (ACP) in the year 2006 [17].
Those are factors related to the patient’s preoperative condition, the surgical
procedure itself, as well as the type of anesthesia delivered and have been
expanded and improved in subsequent studies.
4.4.1 Risk Factors Related to the Patient’s Condition

4.4.1.1 Age
Advanced age has been recognized as a major risk for different adverse
postoperative events [18] and represents the most frequent factor related to PPCs
[17]. Aging may increase the vulnerability of organ systems to a major surgical
stress, or decrease the capability of organ systems to respond to a combination of
multiple minor stressors, which may ultimately compromise their ability to
respond to such challenges [19]. Although such phenomenon, usually known as
frailty, is not exclusive of the elderly patient, it is more often observed in higher
age groups. In fact, advanced age seems to be only a surrogate of frailty, which
is accompanied by an increased pro-inflammatory response in both nonsurgical
[20] and surgical patients [21]. Nevertheless, age still properly stratifies the risk
of PPCs.
4.4.1.2 Functional Dependence

Functional dependence reflects perhaps a relevant degree of disability of a
patient, and as such it is closely related to age and frailty. It has been shown that
this patient-related risk factor and its severity are associated with increased
serum levels of pro-inflammatory markers [22]. Particularly, patients with
advanced age frequently present frailty and some degree of disability with
functional dependence, which further increases the risk for postoperative
complications [23].
4.4.1.3 Classification of the American Society of

Anesthesiologists (ASA)
The ASA classification for general risk evaluation is popular among
anesthesiologists, even if considerable variability among assessors has been
reported in different studies [24, 25]. As a score derived from the degree of
impairment of several organ systems, the ASA classification is unspecific but
has the advantage of integrating possible single factors that may have higher
sensibility for PPCs [9]. However, when taken into account for computing risk of
PPCs, the ASA classification may jeopardize the contribution of relevant risk
factors. Thus, its use as part of risk assessment must be judiciously considered.
4.4.1.4 Smoking
It has been claimed that in lung cancer surgery, the odds of smoking as a risk
factor for PPCs is increased [26]. However, the impact of smoking on the
development of PPCs after thoracotomy [27], even in patients undergoing lung
cancer resection, has been questioned [28]. Therefore, compared to other factors,
smoking seems to play a less important role for PPCs.
4.4.1.5 Respiratory Symptoms

The presence of respiratory symptoms is associated with advanced impairment
of the pulmonary function in obstructive disease [29]. Among those symptoms,
cough, sputum, dyspnea, and wheezing seem to play an important role [30].
4.4.1.6 Peripheral Oxygen Saturation and Pulmonary

Function Tests (PFTs)
Low peripheral oxygen saturation adds importantly to the risk of PPCs following
different types of surgical interventions, including thoracic surgery [11]. Despite
its almost intuitive rationale, this risk factor has been recognized only recently
[9].
In the context of thoracic surgery, PFTs comprehend spirometry and
diffusing capacity of the lung for carbon monoxide (DLCO). According to the
American College of Chest Physicians, impairment of the forced expiratory
volume in one second (FEV1) and DLCO are useful in stratifying the risk of
disability and even mortality following lung resectional surgery [31]. In patients
with lung cancer undergoing surgery, FEV1 represented the PFT parameter that
was better associated with PPCs and better contributed to the risk evaluation
[32]. The predictive value of PFTs holds useful regardless of the surgical
approach, i.e., also for minimally invasive lobectomy [33].
4.4.1.7 Respiratory Infection Prior to Surgery

Infection of the respiratory system in the last month preceding surgery has been
linked to an increased the risk of PPCs [3, 11], but its contribution to predict
these complications has been challenged recently [34].
4.4.1.8 Preoperative Hypoalbuminemia, Weight Loss,

and Body Mass Index (BMI)
These factors are closely related to the nutritional status. Low serum albumin
concentrations seem to increase the risk of PPCs in the general population [17],
possibly to increased incidence of anastomose leakage. In patients undergoing
pneumonectomy, hypoalbuminemia was associated with bronchopleural fistula
formation [35]. Also, weight loss exceeding 10 % in the past 6 months preceding
surgery increases the risk of postoperative pneumonia [36]. Whereas a BMI
<18.5 kg/m2 increases the risk of death after lobectomy for cancer [37], a BMI
>18.5 kg/m2 increases the risk of PPCs after thoracotomy.
4.4.1.9 Preoperative Anemia

Patients with preoperative hemoglobin concentrations <10 g/dL who undergo
lung resection surgery are at increased risk for PPCs [38]. Also in the general
surgical population, anemia adds to the risk of PPCs [3].
4.4.1.10 Chronic Obstructive and Other Pulmonary

Diseases
Chronic obstructive pulmonary disease (COPD) is a comparatively high
prevalent disease [39] that carries a considerable risk for patients to develop both
non-pulmonary and pulmonary postoperative adverse events [40]. This disease
has been incorporated into numerous scores for prediction of risk of PPCs [7,
41–47]. In thoracic surgery patients, COPD is a common comorbidity that
underlies many of the indications for such interventions, for example, lung
volume reduction surgery, bullectomy, and lung transplantation [48], as well as
lung cancer resection and spontaneous pneumothorax surgery [49]. In addition,
the degree of severity of COPD plays a relevant role for prognosis prediction,
since it is associated with increased need for ICU admission following
pulmonary resection [50]. Importantly, the attributable risk of COPD may be
decreased upon pulmonary rehabilitation measures [29]. In the general
population, chronic pulmonary diseases have been implicated in the need for
postoperative reintubation [45].
4.4.1.11 Congestive Heart Failure (CHF)
Congestive heart failure (CHF), even if adequately compensated, adds
considerably to the risk of PPCs in the general surgery population [17, 51]. In
older patients undergoing lung cancer surgery, CHF increased the risk of death
[52].
4.4.1.12 Renal Disease

Patients with renal disease may be at higher risk to develop PPCs [17]. In
surgical patients, acute renal failure increases the need for reintubation and
ventilatory failure [53].
4.4.1.13 Liver Disease

Preoperative liver disease adds to the odds of developing PPCs [11]. In the
general surgical population, cirrhosis is associated with higher risk of death
following surgery [51].
4.4.1.14 Obstructive Sleep Apnea (OSA)

Surgical patients with OSA have an increased risk for postoperative
complications, especially circulatory and pulmonary, also following thoracic
surgery [54, 55].
4.4.1.15 Current Alcohol Use

Alcohol impairs the immune response [56] and causes neurologic impairment,
which may facilitate aspiration and the development of pneumonia
postoperatively. Alcohol use has been identified as a risk factor for development
of PPCs in the general surgical population [17], as is associated with higher risk
of death following pneumonectomy [57].
4.4.1.16 Diabetes Mellitus

Diabetes mellitus has been associated with an increased risk of ARDS following
surgery [44], but it is comparatively less relevant than of other factors. In
patients undergoing lung cancer resection, diabetes mellitus did not increase the
risk of postoperative pneumonia [58].
4.4.2 Procedure-Related and Intraoperative Risk Factors

Thoracic surgery, as compared to other types of surgical interventions, has been
associated with relatively high risk for PPCs in different investigations [3, 17,
44]. This figure is explained by the fact that the intervention itself causes direct
injury to the lungs, the airways, and also the respiratory muscles, likely
interfering with the capability to ventilate, mobilize secretions, and cough. Also,
the presence of atelectasis may impair the gas exchange and lead to hypoxemia.
Certainly, the surgical approach contributes to determine the impact on the risk
of PPCs.
4.4.2.1 Thoracotomy Versus Median Sternotomy

During thoracotomy, the intercostal muscles are likely more injured than during
sternotomy, which could be associated with more severe pain and ventilatory
impairment. In patients undergoing lung cancer resection, median sternotomy
was associated with shorter length of hospital stay, but did not improve survival
[59].
4.4.2.2 Video-Assisted Thoracoscopic Versus Open

Thoracic Surgery
Laparoscopy compared to open surgery has been found to decrease mortality in
the general surgical population [51]. A recent meta-analysis showed that in lung
cancer patients with compromised lung function, lobectomy with video-assisted
thoracoscopy (VATS) is associated with lower risk for pulmonary morbidity than
open surgery [60]. In fact, compared to most open surgical approaches, VATS
has been classified as low risk for postoperative ARDS [44].
4.4.2.3 Extent of Lung Resection

Extensive lung resection may be associated with a shift of the pulmonary
perfusion to the remaining capillary bed, increasing the shear stress to those
areas and consequent failure [61]. In patients undergoing thoracic surgery for
lung cancer, the incidence of acute lung injury was more than three times higher
after pneumonectomy than lobectomy or lesser resections [62].
4.4.2.4 Duration of Surgery

The duration of surgery has been shown to increase the risk of PPCs in different
studies [3, 17, 44, 51]. Particularly, interventions lasting more than 2 h in the
general surgical population [3, 11], or requiring more than 2 h of anesthetic time
for pneumonectomy [63], have been independently associated with an increased
probability of developing adverse pulmonary events.
4.4.2.5 Volatile Versus Intravenous Anesthetics

The anesthesia regimen has the potential to modulate the incidence of PPCs,
given that certain anesthetics promote organ protection. In rats [64], but also in
patients [65], volatile agents compared to intravenous anesthetics reduced lung
injury and/or inflammation. However, up to this date, no randomized controlled
trial demonstrated an advantage of volatile anesthetics in terms of outcome.
4.4.2.6 Muscle Paralysis

The use of neuromuscular blocking agents (NMBAs) for intubation of the
trachea with devices that enable lung separation is almost mandatory, since such
devices are comparatively larger than conventional endotracheal tubes and
optimal conditions more difficult to obtain. Also, NMBAs are used to achieve
optimal thoracic surgical conditions. In the general surgical population,
intermediate-acting NMBAs have been implicated in an increased incidence of
PPCs, especially if reversal of muscle paralysis is not appropriately performed
[66].
4.4.2.7 Restrictive Versus Liberal Fluid Strategy

Liberal fluid strategies have been shown to increase the risk for lung injury after
thoracic procedures. Fluid overload, impairment of lung lymphatic outflow, and
damage of the pulmonary endothelium have been implicated as possible causes
for such complication [67]. A retrospective study in patients undergoing
anatomic lung resections showed that infusion rates exceeding 6 mL/kg/h
increased the risk of PPCs [68].
4.4.2.8 Transfusion of Blood and Blood Products

Transfusion-related acute lung injury (TRALI) is a leading cause of transfusion-
related death. This syndrome is related to the passive infusion of human
leukocyte antigen and human neutrophil antigen, which may elicit an antibody-
mediated [69] inflammatory response, but a non-antibody mediated due to aged
cellular blood products has been also identified [70]. Neutrophils seem to play a
key role in TRALI. Those cells are activated by different insults, for example,
hypotension, mechanical ventilation, or ischemia-reperfusion, which are usually
present in thoracic surgery and serve as a first hit. The transfusion of blood and
blood products leads then to a second hit, with resulting inflammatory response.
4.4.2.9 Mechanical Ventilation

Mechanical stress inflicted by the ventilator to the lung parenchyma has the
potential to cause harm. In patients undergoing esophagectomy, a protective
ventilation with low tidal volume (5 mL/kg, predicted body weight – PBW) with
positive end-expiratory pressure (PEEP) of 5 cmH2O was associated with less
lung inflammation than a non-protective mechanical ventilation with high tidal
volume (10 mL/kg PBW) with PEEP of 0 cmH2O [71]. In a retrospective study
in lung cancer patients, intraoperative ventilation with lower plateau inspiratory
pressure was associated with a decreased incidence of acute lung injury [62]. In
addition, a recent meta-analysis showed that protective compared to non-
protective ventilation reduced the incidence of postoperative lung injury
following abdominal and thoracic surgery. Since the term “protective
ventilation” is not well defined and mostly seen as a bundle of measures (low
tidal volume, PEEP, recruitment maneuvers, low inspiratory oxygen fraction), it
is not clear which of those elements are responsible for lung protection.
Apparently, low tidal volumes play an important role in lung protection, whereas
the relevance of PEEP has not been demonstrated [72].
4.5 Predictive Models of Postoperative Pulmonary

Complications in Thoracic Surgery
Several predictive models of postoperative complications have been developed,
but only a few of them are specific for the thoracic surgery population and
pulmonary complications. Those scores usually are limited by one or more of the
following factors: (1) use of preoperative variables only; (2) lack of clearness of
the model’s development as listed in the STROBE guidelines and defined
according by the “Transparent Reporting of a Multivariable Prediction Model for
Individual Prognosis or Diagnosis (TRIPOD)” statement [73]; (3) lack of
external validation in independent studies; (4) lack of generalizability to other
patient populations; and (5) lack of capability of predicting the outcome of
individual patients, rather than groups. However, they still build the fundament
for stratification of patients for testing interventions, allocation of resources,
benchmarking, and also professional audits. Moreover, for the treating physician,
they may be helpful to justify and obtain informed consent for certain procedures
on a more objective risk/benefit analysis basis. Also, they might contribute to
improve a patient’s condition depending whether potentially modifiable risk
factors are involved in a poor prognosis. In this subsection, we will briefly
describe a few relevant scoring systems for prediction of PPCs, with emphasis in
the application in noncardiac thoracic surgery.
4.5.1 The Physiological and Operative Severity Score for

the Enumeration of Mortality and Morbidity (POSSUM)
The POSSUM score, which is based on 12 preoperative factors, was originally
developed for predicting adverse outcome in the general population [74]. In
patients undergoing lung resection, the POSSUM scoring system showed
acceptable performance for predicting PPCs [75].
4.5.2 The Cardiopulmonary Risk Index (CPRI)

The CPRI combines cardiopulmonary variables into one single score ranging
from 1 to 10, where 10 represents the worst value. In patients undergoing
pneumonectomy, but not other types of thoracic surgery, a CPRI ≥4 was
associated with increased incidence of PPCs [76].
4.5.3 The Expiratory Volume Age Diffusion (EVÁD)

Capacity Score
The EVÁD score uses three main covariates to assess the risk of complications
after lung resection, namely, age, spirometry, and diffusing capacity [77].
Compared to the CPRI and POSSUM scoring systems, EVÁD showed a better
predictive value for PPCs after major lung resection.
4.5.4 The Postoperative Respiratory Failure (PRF) and

the Postoperative Pneumonia Risk (PPR) Index
The PRF index has been developed within a retrospective analysis of patients
admitted to the National Veterans Affairs Surgical Quality Improvement
Program (NSQIP) [7] and is able to identify high-risk patients with a 30 %
likelihood of developing respiratory failure. Later on, a score to predict
pneumonia was proposed by the same group and using NSQIP data, which
applies also to patients undergoing thoracic surgery [36]. Both the PRF and PPR
indices, with 7 and 14 predictors, respectively, have not been validated
externally.
4.5.5 The Assess Respiratory Risk in Surgical Patients in
Catalonia (ARISCAT) Score
The ARISCAT score is a specific predicting tool for PPCs [3]. It has been
developed in a European region only (Catalonia, Spain) but undergone extensive
recalibration and external validation in a large cohort from different countries,
the so-called Prospective Evaluation of a RIsk Score for postoperative
pulmonary COmPlications in Europe (PERISCOPE) study [11]. Furthermore,
the PERISCOPE study identified also a group of preoperative variables that
allow the prediction of postoperative respiratory failure (PERISCOPE-PRF
score) [34]. To date, the ARISCAT score, as recalibrated in the PERISCOPE
study, represents one of the most valuable tools for prediction of PPCs.
However, it has not been specifically developed for thoracic surgery and
therefore does not address some particular complications that may occur in such
population, for example, persistent leakage of the operated lung. Furthermore, it
is not clear how some of the elements of the collapsed composite PPC, for
example, pneumothorax and lung edema, should be dealt with if they occur in
the operated hemithorax. Also, intraoperative variables other than duration of
surgery are not taken into account.
4.5.6 Preoperative and Intraoperative Predictors of

Postoperative Acute Respiratory Distress Syndrome
Postoperative ARDS probably represents the most severe form of PPC. Using
data from a single US center, investigators developed a score for predicting
ARDS in the general surgical population, which may find application also in
thoracic surgery [41]. One important advantage of that score is that preoperative
and intraoperative predictors have been identified. However, the lack of external
validation still poses doubt about its generalizability.
4.5.7 Further Scoring Systems Developed from Single-

Center Databases
A number of prediction scoring systems have been developed, which could be
useful in the field of thoracic surgery. They addressed the need for unplanned
postoperative tracheal intubation [43, 45], as well as the development of
postoperative acute lung injury [44]. Recently, a prediction rule for estimating
PPCs has been proposed [47], but patients undergoing pulmonary surgery have
been excluded a priori.
4.6 Summary
PPCs are common after thoracic surgery. Usually, the term PPC is defined not as
a single complication, but rather a collapsed composite that consists of mild,
moderate, and severe complications. Despite differences in severity, they
increase the length of stay in hospital and even mortality, especially when two or
more complications are present. Preoperative but also intraoperative factors have
been identified that are associated with an increased risk for PPCs after thoracic
surgery. Those factors, which have been drawn from retrospective, observational
prospective, single- and multiple-center studies, have combined by multivariable
analyses into scores that might be useful to predict the risk of developing PPCs.
Some of those scores addressing general surgical populations have undergone
extensive external evaluation in separate studies, whereas others have focused on
thoracic surgical patients, but not been validated so far. Albeit the ideal score for
predicting PPCs after thoracic surgery has not been developed and validated yet,
the available tools already allow the estimation of the risk of pulmonary adverse
advents in this surgical population.
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DOI 10.1007/978-3-319-19908-5_5
5. Fluid Management During and After the

Operation: Less Is More or More Is Less?
Catherine Ashes1 and Peter Slinger2
(1) Department of Anaesthetics, St Vincent’s Hospital, Fitzroy, Darlinghurst,
NSW, Australia
(2) Department of Anesthesia, Toronto General Hospital, Toronto, Canada

Peter Slinger
Email: Peter.Slinger@uhn.ca
5.1 Introduction
Acute lung injury is a major cause of mortality after lung resection surgery [1],
and a principle focus of the thoracic anesthesiologist is prevention of this
devastating complication. Fluid therapy is an integral component of the
perioperative management of these complex patients [2], and the risks of fluid
overload and tissue edema must be balanced against the risk of hypovolemia and
end-organ ischemia [3].
5.2 Epidemiology and Impact of ALI/ARDS After Lung
Resection Surgery
Post-pneumonectomy pulmonary edema (PPPE) was first described in 1984 by
Zeldin et al. [4], where ten cases of lung injury following pneumonectomy were
described. It has since been recognized that the syndrome may occur after lesser
degrees of resection and surgery requiring one-lung ventilation (OLV) without
lung resection [5, 6]. PPPE has been found to share histological features with
acute respiratory distress syndrome (ARDS) [7], is not of cardiogenic origin [3],
and the most severe form of PPPE follows a course indistinguishable from
ARDS [5]. Accordingly, the condition may be described as post-thoracotomy
acute lung injury (ALI) or ARDS. Post-thoracotomy ALI is generally classified
by the American-European Consensus on ARDS criteria [8].
While the incidence of lung injury after lung resection is fairly consistent,
between 2 and 4 % [9–11], the mortality rate has decreased from almost 100 %
to less than 40 %, largely due to improvements in ICU management [1]. The
mortality rate is higher with ARDS than ALI [5].
The risk factors for perioperative ALI most consistently reported are more
extensive resections (such as pneumonectomy) and fluid overload [5, 9]. Other
pre- and intraoperative factors have also been implicated, including ASA class
[12, 13], alcohol abuse [9, 13], previous radiotherapy [14], low predicted
postoperative lung function [15], non-protective ventilation strategies [16], and
right pneumonectomy [7, 17].
5.2.1 Fluid Administration as a Risk Factor

In the landmark study by Zeldin et al. [4], patients who received a large fluid
load (4913 ± 1169 mL, n = 10) in the first 24 h following pneumonectomy had a
higher incidence of PPPE than those receiving less fluid (3483 ± 984, n = 15
controls). These findings were corroborated by a canine right pneumonectomy
model, which compared three groups: a liberal crystalloid load (100 mL/kg bolus
preoperatively, followed by >100 ml/kg postoperative balance), a judicious load
(50 mL/kg bolus preoperatively followed by <100 mL/kg balance), and a control
group (the same fluid regimen as the liberal pneumonectomy group and sham
thoracotomy). Pulmonary edema ensued in all of the liberal pneumonectomy
dogs, however, in neither of the other groups. This implies that it is not only the
volume of fluid administered that predisposes to ALI but that the local and
systemic changes that occur at lung resection contribute significantly to the
pathophysiology of the condition.
Subsequently, fluid administration, both intra- and postoperatively, has
repeatedly been found to be a risk factor for the development of ALI after lung
resection [9, 12, 14–17] (see Table 1). Fluid in excess of 2 L total volume
administered during pneumonectomy is linked with negative effects on
postoperative respiratory outcomes [3, 12, 14, 16], and similar results have been
demonstrated with high perioperative fluid loads and lesser pulmonary
resections [3, 9, 15]. In patients with pulmonary fibrosis, higher perioperative
fluid volumes and balance are linked to an increased risk of postoperative
respiratory compromise after lung resection surgery, a devastating complication
[18]. Similar findings have also been demonstrated in esophagectomy; however,
in these patients, larger volumes of fluid (in the order of 5 L) are implicated [6,
19
Table 5.1 Fluid administration in lung resection and esophagectomy patients with and without
postoperative acute lung injury
Authors Procedure Number Study design Timing Acute No acute P value
(publication of lung lung
year) patients injury injury
fluid fluid
volume volume
Zeldin et al. Pneumonectomy 25 Retrospective 24 h 37 mL/kg 27 mL/kg <0.05
(1984) [4] postoperative
infusion
Parquin et Pneumonectomy 146 Prospective Intraoperative ≥2.0 L <2.0 L <0.01
al. (1996) (observational)
[14]
Licker et al. Pulmonary 879 Retrospective Intraoperative 9.1 7.2 0.023
(2003) [9] resection mL/kg/h mL/kg/h
Cumulated 2.6 2.0 0.003
intra- and 24 h mL/kg/h mL/kg/h
postoperative
Fluid balance 2.0 L 1.52 L 0.026
24 h
postoperation
Fernández- Pneumonectomy 170 Retrospective Intraoperative 2.2 L 1.3 L 0.001
Pérez et al.
(2006) [16]
Alam et al. Pulmonary 1428 Retrospective Intraoperative 2.775 L 2.5 L <0.05
(2007) [15] resection and 12 h
postoperative
Marret et al. Pneumonectomy 1200 Retrospective Intraoperative 3.8 L 2.5 L <0.0001
(2010) [12]
Mizuno et Pulmonary 52 Retrospective Intraoperative 7.71 10.3 0.049
al. (2012) resection total volume mL/kg/h mL/kg/h
[18] (pulmonary Intraoperative 4.99 8.00 0.035
fibrosis patients) fluid balance mL/kg/h mL/kg/h
Casado et al. Esophagectomy 45 Retrospective Intraoperative 5.415 L 4.174 L 0.01
(2010) [6] fluid balance
Fluid balance 5 7.873 L 5.928 L 0.03
day
postoperatively
Tandon et al. Esophagectomy 168 Retrospective Intraoperative 5.0 L 4.4 L <0.027
(2001) [19]
].
The incremental volume of fluid required to increase the risk of ALI is not
large. It is evident from the study by Licker et al. [9] that there may be a small
margin between a more “liberal” strategy (the volume of fluid administered that
is associated with ALI) and a “conservative” approach (the volume of
administered fluid not associated with ALI) [20]: while there was a significant
difference in outcomes between patients receiving larger volumes of
intraoperative fluid (9.1 v 7.2 ml/kg/h), higher positive fluid balance in the 24 h
following surgery (2.0 v 1.52 L), and higher accumulated intra- and
postoperative fluid volume (2.6 v 2.0 L), the differences are not great.
Furthermore, a “dose-dependent” relationship between perioperative fluid
administration and ALI was demonstrated by Alam et al. [15], who found that
for every 500 mL of perioperative fluid administration, there was a significant
increase in the rate of primary lung injury (OR 1.2 (1–1.4), p = 0.02).
5.3 Pathophysiology
A “multiple-hit hypothesis” for lung injury is well described for ARDS [21]. It
describes a number of pathophysiological insults, which, in isolation, may not
result in lung injury, however, when accumulated result in the clinical syndrome
of ALI or ARDS. The “multiple-hit hypothesis” is likely to also be relevant in
perioperative ALI. The “first hit” is an activation of the systemic inflammatory
response by surgical trauma, manipulation, or atelectasis [22], which
subclinically injures the lung, rendering it more susceptible to subsequent
insults. The successive hits then damage the already vulnerable alveolar-
capillary membrane, leading to overt ALI or ARDS. The putative second hit may
be a variety of known risk factors for postoperative ALI such as FFP
administration [13], mediastinal lymphatic damage [23], non-protective
ventilation strategies [16], and oxygen toxicity [24].
This multiple-hit model for perioperative ALI is supported by a rodent
model, which used intratracheal lipopolysaccharide to mimic sepsis-induced
lung injury. A small lung injury was observed with either OLV and
pneumonectomy or lipopolysaccharide alone, but an exaggerated injury was
triggered when OLV, pneumonectomy, and lipopolysaccharide were combined in
one animal [25]. This suggests that the lung is “primed” by the initial insult, and
then a subsequent insult will potentially result in a more severe, clinically
evident manifestation.
5.3.1 Revised Starling Equation and the Endothelial

Glycocalyx
For generations, the axiom guiding transcapillary fluid behavior was Starling’s
model, first proposed in 1896 [26]. The model expresses fluid flux as a balance
between opposing hydrostatic and oncotic pressures. Along the length of the
capillary filtration is favored at the arteriolar end and reabsorption at the venular
end.
However, in vitro and in vivo deviations from the classic Starling principle
have been noted [27], such as absence of the venous reabsorption [28] and
lymphatic flow [29] required to prevent interstitial edema, and lack of
importance of the interstitial colloid osmotic pressure in determining
transendothelial fluid balance [30]. This led to further investigation into non-
Starling mechanisms of barrier regulation involving the endothelial glycocalyx
layer (EGL) [31].
Danielli first proposed the existence of the EGL in 1942 [32]. It is a dynamic,
fragile, and complex layer of membrane-bound macromolecules at the luminal
surface of the vascular endothelium [31]. The composition and thickness of the
glycocalyx change constantly, as it is continually sheared by plasma flow and
replaced [33]. Its components have a net negative charge and therefore repel
negatively charged molecules and blood cells [34].
A primary function of EGL is to regulate and influence vascular permeability
[35]. Together with circulating substances, it forms a barrier that prevents
circulating cells and macromolecules from entering the interstitium. In contrast
to the original Starling model, which explained regulation of fluid balance
occurring across the entire endothelial cell, a revised model has been proposed
whereby the hydrostatic and osmotic forces act only across the EGL surface
layer on the luminal aspect of the endothelium [30]. These forces reach
equilibrium very quickly, resulting in a much lower fluid flux than predicted by
the traditional Starling equation (see Fig. 5.1).
Fig. 5.1 The glycocalyx model for fluid exchange between the intravascular (c) and interstitial (i) spaces.
The various components of the endothelial glycocalyx layer (EGL) and revised Starling’s forces are shown.
In steady state, net filtration into the interstitium occurs and is subsequently removed by the lymphatic
system. EC endothelial capillary cells, π oncotic pressure, P hydrostatic pressure, g subglycocalyx space
(Reproduced with permission from: Ashes and Slinger [3])
The EGL has other functions. It regulates blood cell-endothelial interaction

by its negative charge and via specific adhesion molecules for leukocytes and
platelets. These are normally hidden deep within the glycocalyx structure, but
become exposed following damage to the EGL [35]. It also protects the vascular
endothelium from shear stress and oxidative damage, via nitric oxide-induced
vasodilation [36] and scavenging of oxygen free radicals [34].
The EGL may be injured by inflammatory cytokines [37], surgical trauma,
and ischemia-reperfusion [38]. Hypervolemia damages the EGL, both by
dilution of plasma proteins and via release of atrial natriuretic peptide, which
strips the EGL [38]. Loss of the intact EGL causes increased vascular
permeability and fluid extravasation. Loss of plasma proteins further compounds
this. Leukocyte adhesion molecules are exposed, promoting cellular adhesion,
migration, and further inflammation [39]. This vicious cycle of increased
permeability, extravasation, and inflammation leads to pulmonary edema, as is
observed in ALI.
Several empiric strategies, based on animal experiments, have been proposed
to protect the EGL, including avoiding hypervolemia, albumin infusion [40],
corticosteroids [41], antithrombin III [42], and direct inhibitors of inflammatory
cytokines [43]. Volatile anesthetic agents, when compared with propofol, have
been associated with less local release of inflammatory mediators [44, 45] and
less glycocalyx destruction [46] (see Fig. 5.2).
Fig. 5.2 Electron microscopic views of hearts stained to reveal the glycocalyx. (a) An intact glycocalyx
after 25 min. Of nonischemic perfusion. (b) A residual endothelial glycocalyx after 20 min of warm
ischemia and 10 min consecutive reperfusion. (c) The glycocalyx after pretreatment with 1MAC of
sevoflurane followed by 20 min of warm no-flow ischemia and 10 min reperfusion (Reproduced with
permission from: Chappell et al. [46])
5.3.2 Pulmonary Endothelial Damage

The alveolar endothelium also plays a role in the regulation of pulmonary
interstitial fluid balance. Fluid transport across the endothelium may occur via
tight junctions, breaks in tight junctions and vesicular transport [47]. Leaky
junctions are associated with cell death and allow passage of larger molecules.
Epithelial sodium channels (ENaCs) are able to enhance the clearance of
alveolar fluid [47], and they may be stimulated by beta-adrenergic agonists [48].
Endothelial damage has therefore been implicated in the pathogenesis ALI
after lung resection surgery. Endothelial injury maybe induced by activation of
systemic and local inflammatory mediators, related to positive pressure
ventilation; “volutrauma;” oxygen toxicity; ischemia-reperfusion injury; surgical
trauma; and preexisting lung disease [1, 3]. Endothelial cell injury results in
disruption of intercellular endothelial cell junctions, cytoskeleton contraction,
and cell death, leading to increased permeability of the alveolar-capillary barrier
and decreased lung compliance [1].
5.3.3 Lymphatics and RV Dysfunction

Although fluid overload is well recognized as a risk factor for ALI after thoracic
surgery, there also appear to be other factors at play. ALI may still occur when
very strict fluid-restrictive strategies are implemented [49].
Lung lymphatics play a key role in fluid clearance from the lung [47].
Capillary filtrate that enters the interstitium is drained by lymphatics, and when
their capacity to drain fluid is exceeded, pulmonary edema will occur [3].
Although lymph flow can increase sevenfold in response to elevated interstitial
pressure [50], in the perioperative setting, this capacity may be reduced. Surgical
trauma related to lung resection surgery is thought to be an important factor
influencing this [3]. Pulmonary lymphatic drainage is not symmetrical: the
drainage of the right lung is essentially ipsilateral (>90 %), whereas the left lung
has a significant contralateral contribution (>55 %) [51]. Therefore, right
pneumonectomy confers a significantly higher risk of pulmonary edema in the
left lung, as over half its lymphatic drainage will be lost, which has been
demonstrated clinically [7, 17].
Lymphatic drainage may be further impaired by postoperative right
ventricular (RV) dysfunction: the resultant elevation in central venous pressure
will reduce the drainage capacity of the lymphatic system [52]. RV dysfunction
is very common after lung resection surgery, particularly pneumonectomy [53],
and is thought to relate to increased RV afterload and tachycardia [54, 55].
5.4 Risks of Restrictive Approach: Tissue

Hypoperfusion and AKI
A restrictive approach to fluid management has been widely adopted to prevent
ALI after thoracic surgery [47]. However, a restrictive fluid regimen may incur
the risks associated with hypovolemia, which include impaired end-organ
perfusion, in particular, acute kidney injury (AKI) [3, 47].
Recent data suggest the incidence of AKI after lung resection surgery is 5.9–
6.8 % [56, 57]. It is associated with increased hospital length of stay [56] and
cardiopulmonary complications [57]. A link to increased mortality has been
inconsistent [56], although a recent study demonstrated a mortality of 19.8 % in
those with AKI [57].
Many risk factors for AKI have been identified. Studies by Licker et al. [1]
and Ishikawa et al. [56] each identified multiple factors associated with AKI
after lung resection surgery. Preoperative patient characteristics include ASA
class 3 or 4, FEV1, hypertension, peripheral vascular disease, preoperative renal
dysfunction, and preoperative use of angiotensin II receptor antagonists.
Intraoperatively, use of vasopressor, duration of anesthesia, use of colloids, and
open procedures were implicated. The amount of fluid given intra- and
postoperatively was not found to be associated with an increased incidence of
AKI: Licker et al. [57] found that patients with and without AKI received similar
volumes of fluid both intraoperatively (4.8 v 4.9 mL/kg/h) and on postoperative
day 1 (1.1 v 1.1 mL/kg/h), respectively. Similarly, Ishikawa et al. [56] found
similar volumes of fluid administered intraoperatively in patients with and
without AKI (1450 v 1276 mL).
Maintenance of adequate perfusion pressure is an important factor in
preventing AKI [3], especially in those at increased preoperative risk related to
chronic kidney disease, hypertension, or peripheral vascular disease.
Hypotension related to excessive anesthesia should be avoided, and depth of
anesthesia monitoring may allow more accurate dose titration. Adequate
perfusion pressure should be maintained through judicious use of vasopressors,
and invasive hemodynamic monitors may provide valuable information to help
guide therapy [3].
5.5 Esophagectomy
In esophagectomy, the traditional approach involved aggressive fluid
resuscitation, due to postulated “third space” losses [3]. The third space, first
described in 1961 in major abdominal surgery [58], is classically thought to be a
fluid compartment anatomically and functionally separate to the intravascular
space, not involved in the exchange of fluid between the vascular space and the
interstitium [59]. However, the exact location of this hypothetical compartment,
thought to be the gastrointestinal tract or traumatized tissues, has never been
fully elucidated. Its existence has recently been challenged due to weak initial
evidence, flawed methodology, and the emergence of new data measuring
extracellular fluid volume in surgery and hemorrhage [60].
There is an association between fluid balance and postoperative
complications after esophagectomy. A link between higher perioperative positive
fluid balance and cardiorespiratory complications and death has been
demonstrated [61]. Fluid restriction seems protective against respiratory
complications following esophagectomy, both as a sole factor [62], and as part of
a standardized multimodal regimen including thoracic epidural analgesia, early
extubation, and modest fluid restriction [63]. Due to the systemic inflammatory
state that occurs following major surgery, and the increased capillary
permeability that ensues, irrational replacement of putative “third space” losses
during esophagectomy will lead to fluid accumulation in the interstitial space
and therefore pulmonary edema [3].
Fluid administration may adversely affect surgical outcomes. There is a
growing pool of data suggesting that surgical outcomes [64, 65] including
anastomotic complications [66, 67], following gastrointestinal surgery, may be
improved with a restrictive fluid strategy or multimodal perioperative
management protocol that includes fluid restriction. There is no specific
evidence of anastomotic protection by a restrictive fluid regimen in esophageal
resection; however, extrapolation of these findings suggests that there may be
some additional benefit incurred by fluid restriction in esophagectomy, both
improving surgical outcomes and reducing the risk of ALI.
There has been concern regarding use of vasopressors in esophagectomy, due
to fear of anastomotic ischemia, a major cause of postoperative mortality. In a
porcine model, norepinephrine, when used to treat hypotension caused by
hemorrhage, has been associated with severe graft hypoperfusion [68]. However,
a small human study found that epinephrine, used to treat hypotension caused by
thoracic epidural bupivacaine, restored the resultant decrease in anastomotic
blood flow [69]. Similarly, in another small human study, phenylephrine infusion
was found to correct epidural bolus-induced reduction of blood flow at the
anastomotic end of the newly formed gastric tube [70]. Therefore, it is likely that
vasoactive agents, when used to counteract hypotension induced by general or
neuraxial anesthesia, can be used without jeopardizing the viability of the
surgical anastomosis.
5.6 Goal-Directed Approaches

Goal-directed therapy has been used with variable success in cardiac, vascular,
orthopedic, and major abdominal surgery. Interest was generated by Shoemaker
et al. [71], who demonstrated morbidity and mortality benefits when a goal-
directed approach was applied to the perioperative care of high-risk surgical
patients. Some subsequent studies have shown reduced risk of infective
complications [72], AKI [73], cardiovascular complications [74], pneumonia,
and hospital length of stay [73]. However, others have found no benefit, in
abdominal aortic surgery [75] or colorectal surgery [76]. In fact, a goal-directed
approach was associated with negative effects on hospital length of stay and
readiness for discharge in a subset of aerobically fit colorectal surgical patients
[76].
It has been suggested that using clinical assessment of cardiac preload to
guide fluid therapy may reduce the risk of ALI after thoracic surgery [3, 47, 77]:
by optimizing the volume of fluid infused, the risks of both fluid overload and
ALI and hypovolemia and AKI may be reduced. However, it should be noted
that studies of goal-directed therapy in non-thoracic surgery frequently feature
more “aggressive” fluid resuscitation in the treatment arm, with patients
undergoing goal-directed therapy receiving significantly more fluid than those in
the control arms [78–80]. This is at odds to the traditional approach of fluid
restriction in thoracic surgical patients already discussed.
Preload estimation is notoriously challenging. Commonly used pressure
measurements, such as central venous pressure (CVP) and pulmonary artery
occlusion pressure (PAOP), are indirect surrogates for LVEDV and as such are
influenced by many other factors, including intrathoracic pressure variation
(such as in positive pressure ventilation and OLV), open chest surgery, RV
function, and cardiovascular compliance [77]. Most goal-directed strategies
utilize monitoring of hemodynamic parameters that predict fluid responsiveness,
defined as a significant increase in cardiac output with fluid loading, which
theoretically allows maximization of cardiac performance and avoids
unnecessary volume administration.
5.6.1 Cardiac Index Estimation

Many goal-directed protocols target cardiac index, which may be measured
using a variety of modalities, including the pulmonary artery catheter,
transpulmonary thermodilution (e.g., PiCCO monitor), pulse contour analysis
(e.g., FloTrac-Vigileo system), and transesophageal Doppler measurement.
Although use of esophageal Doppler is impractical in esophageal surgery, it has
been used with good effect in lung resection surgery. Esophageal Doppler was
able to detect a reduction in stroke volume index in lung resection surgery,
despite unchanged heart rate and mean arterial pressure, and was used to guide
hemodynamic support and fluid therapy [81].
5.6.2 Dynamic Variables: Stroke Volume Variation

(SVV) and Pulse Pressure Variation (PVV)
SVV and PPV both use the heart-lung interaction, integrating the effects of
preload, respiratory variation, and blood pressure to assess fluid responsiveness
[3, 47]. There are some theoretical limitations to the use of these indices during
thoracic surgery. Firstly, there has been concern regarding their validity during
open chest conditions [82]. Secondly, due to the dependence of these
measurements on respiratory variation, their accuracy also is dependent on tidal
volume. At relatively large tidal volumes of 8–10 mL/kg during two lung
ventilation (TLV), SVV ≥ 12 ml/kg and PPV ≥ 10 mL/kg correlate highly with
fluid responsiveness [83]; however, ventilation with a lung protective strategy
may not have the same correlation. Thirdly, the volume of shunted blood through
the non-ventilated lung should not contribute to the generation of SVV and PVV,
necessitating a lower threshold value during OLV than that used during TLV [3,
84]. In one study examining SVV during OLV, it was shown only to be
acceptably predictive of volume responsiveness with tidal volumes >8 mL/kg,
with a threshold for fluid responsiveness of 10.5 % [85]. At the upper limits of
fluid responsiveness, small increases in cardiac output are associated with large
increases in extravascular lung water. This is particularly a problem in conditions
of increased endothelial capillary permeability (see Fig. 5.3) [84].
Fig. 5.3 Superimposition of the Frank-Starling (green) and Marik-Phillips (blue) curves demonstrating the
effects of increasing preload on stroke volume (SV) and extravascular lung water (EVLW) in a patient who
has a large increase in preload responsiveness (a) vs. a small increase in preload responsiveness (b). With
conditions of increased capillary permeability such as sepsis, the EVLW curve is shifted to the left, and
small increase in preload can result in large increases in EVLW. CO cardiac output (Reproduced with
permission from: Marik and Lemson [84])
SVV has been used successfully to guide fluid therapy in thoracic surgery. A
randomized study in thoracoscopic lobectomy found that the goal-directed
therapy group, who received fluid boluses guided by SVV using the FloTrac-
Vigileo system, had higher PaO2/FiO2 ratios at the end of OLV, earlier
extubation time, and received less overall fluid (1385 ± 350 mL vs. 985 ± 135
mL) [86]. During esophagectomy, SVV accurately predicted hypovolemia, was
useful as a guide to appropriately time perioperative fluid therapy, and correlated
better with cardiac output than CVP [87].
5.6.3 Early Detection of Pulmonary Edema

Transpulmonary thermodilution technology has the added advantage of enabling
calculation of extravascular lung water (EVLW) and therefore quantification of
pulmonary edema [88]. EVLW has been shown to be an independent predictor of
prognosis and survival in critically ill patients [89] and in esophagectomy has
been found to correlate with PaO2/FiO2 ratio, pulmonary compliance, lung
injury score [90], and pulmonary complications [91]. EVLW is derived by
subtracting the pulmonary blood volume (PBV) from the pulmonary thermal
volume (PTV); there has therefore been concern regarding the use of EVLWI
after lung resection, as both PBV and PTV may change [92]. However, EVLWI
measured by PiCCO has been shown to correlate well with a double-dye
technique for up to 12 h after following major lung resection [93]. A study
assessing a goal-directed approach to fluid management for thoracic surgery
requiring lateral thoracotomy and OLV found that their strategy, fluid
management guided by SVV, did not result in pulmonary fluid overload as
assessed by PiCCO EVLWI [94].
Lung ultrasound has been used to diagnose pulmonary edema by the
presence of ultrasound B-lines (previously “ultrasound lung comets”) with a
high degree of sensitivity and specificity (97 % and 95 % respectively) [95]. B-
lines may also be quantified, with good inter-rater reliability [96], and there is a
correlation between the number of B-lines and EVLW in patients following
cardiac surgery [97]. In ARDS, a significant correlation between ultrasound B-
lines score and EVLW was shown, with a B-lines score ≥6 indicating a
pathologic EVLW >10 mL/kg (sensitivity 82 %, specificity 77 %) [98]. There is
very little data evaluating this technique for quantitative assessment of ALI [99],
and no study to date addresses its application in the perioperative setting.
However, lung ultrasound represents a promising noninvasive bedside modality
to rapidly assess EVLW of patients at risk of perioperative lung injury, including
those undergoing thoracic surgery, and as such warrants further investigation in
the perioperative setting.
5.7 Fluid Choice

Fluid choice in thoracic surgery remains controversial, with concerns regarding
unwanted extravascular distribution of crystalloids to the interstitial space
balanced against known adverse effects of the various colloid solutions,
including AKI, coagulopathy, and anaphylaxis.
Hyperoncotic colloids have been advocated for use in ALI, due to their
potential to promote shift of extravascular lung water into the intravascular space
[47]. Some beneficial effects on pulmonary parameters have been demonstrated,
including pulmonary permeability [100, 101], histological findings [102],
reductions in VILI and pulmonary edema [103], and more rapid hemodynamic
stabilization [101]. However, in a large systematic review of burns, trauma, and
surgical patients, no outcome benefit of colloids could be demonstrated, and
hydroxyethyl starch (HES) was found to possibly increase mortality [104].
There is particular concern regarding HES and the risk of AKI: in a
multicenter RCT of patients with severe sepsis, HES was shown to increase risk
of mortality and use of renal replacement therapy [105]. These findings were
seemingly confirmed when a recent systematic review and meta-analysis of HES
in critically ill patients found that HES use was associated with a significantly
increased risk of AKI, use of renal replacement therapy, and death [106].
Due to concerns regarding synthetic colloid therapy, interest in human
albumin has been renewed, as there is no evidence of adverse effects on renal
function, and it is generally felt not to affect coagulation [107]. The SAFE trial
[108] failed to demonstrate any difference between 4 % albumin and saline
therapy in a variety of outcomes in a mixed population of critically ill patients. A
recent systematic review and meta-analysis comparing albumin to saline therapy
in patients with ARDS found no significant mortality difference, but improved
PaO2/FiO2 in the first 48 h and after 7 days in patients receiving albumin [109].
However, an overall paucity of evidence was noted, and there is clearly a need
for more randomized controlled trials to address this question.
Conclusion
Postoperative ALI is a devastating complication of thoracic surgery. New
insights into its pathophysiology include the multifactorial risk profile and the
role of the EGL. Excessive fluid administration is harmful, and the risk of ALI
may be reduced by fluid restriction, without jeopardizing end-organ perfusion.
Several new concepts will continue to be explored, including goal-directed
therapy, bedside assessment of EVLW, and fluid selection.
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DOI 10.1007/978-3-319-19908-5_6
6. How to Organise the PACU? What to

Treat in the PACU?
Mohamed R. El Tahan1
(1) Anaesthesiology Department, College of Medicine, University of
Dammam, Dammam, Saudi Arabia

Mohamed R. El Tahan
Email: moham-edrefaateltahan@hotmail.com
6.1 How to Organise the PACU?

The implementation of the PACUs has gained the attention of healthcare
providers since 1942 to improve patient safety and reduce the incidence of
postoperative anaesthesia-related complications, mortality and length of hospital
stay [1]. The economic structure of the PACU is likely to decrease the hospital
costs [2]. The PACU’s advantages are extended to patients undergoing thoracic
procedures, because the PACU has highly specialised facilities and essentially
functions as an ICU. Thus, increased availability of the PACU beds resulted in
reduced utilisation of ICU resources without compromising patient care after
major thoracic surgery [3].
6.1.1 PACU Location

Importantly, the PACU should be located in immediate proximity to the OR,
assuming that both are on the same floor, to provide instant access to essential
supplies and equipment and allow the surgical and anaesthesia personnel who
recently cared for the patient, in timely identification and treatment of any
significant complications during the PACU stay. Unfortunately, this may not
always be possible due to pre-existing architecture or construction limitations.
The straight path versus multiple turns as well as the short distance should be
considered during the construction of the PACU to facilitate the transfer from the
OR to the PACU. Whereas the elevator trips during the transfer from the OR to
the PACU should be avoided as much as possible to minimise the potential delay
and harm for the patients. Before finalising the construction plans, the
responsible anaesthesiologists should determine the time needed to transfer from
the most distant OR to the PACU door while pushing a stretcher and several IV
poles with infusion pumps [4].
6.1.2 Number of PACU Bed Slots

The appropriate number of PACU bed slots varies with the type and length of
surgical cases (e.g. the first cases are likely be discharged from the PACU before
second cases are finished), and the usual turnover time of both the OR and
PACU beds. Thus, it is recommended that 1.5–2 PACU slots should be available
for each room in the OR suite [4].
6.1.3 PACU Floor Plan

A traditional design is a square open-ward design with one wall accommodating
the nurses’ desk and support areas (e.g. medication carts or cabinets, seating area
for order writing or dictation, equipment and supply storage, linen carts, etc.)
and the other three walls having patient bed slots (Fig. 6.1). Supplies are usually
stored on shelves or in baskets on the head wall (Fig. 6.2). This design offers
direct, simultaneous sight lines to the patients and the shortest distance between
the PACU beds to avoid untoward clinical events or demand to increase nursing
staff.
Fig. 6.1 (a, b) A traditional PACU square open-ward design, (c) the PACU bed-spaces and [white arrows]
the standard bright fluorescent ceiling lights
Fig. 6.2 The stored PACU supplies in baskets on the head wall
The available designs for the patient’s bed slots include:

Lined up along a wall where the utilities come from the wall by the
patient’s head (Fig. 6.1).
“Pods” of four beds at 90° angles located in the middle of a large space.
The utilities drop from the ceiling or come up into a tower-like utility tree at
the centre of the four patients’ heads allowing one or two nurses to have
immediate access to deliver care with little time or effort lost walking from
bed to bed [4].
Additionally, the design of the PACU must accommodate permanent and
prominent places for emergency carts (resuscitation, airway and surgical
equipment particularly for thoracic patients) (Fig. 6.3) and a significant storage
space (Fig. 6.4a–c).
Fig. 6.3 The emergency PACU cart
Fig. 6.4 The storage space in the PACU. (a) Cabinets including blankets, linens and fluids; (b) drawers
including commonly used medications in the PACU; and (c) a cabinet and a cart including medications
Ideally, there should be at least one isolation room that has a connecting door
with the main PACU area and another door opening out to a hospital corridor,
allowing separation patients with resistant infections or severely
immunocompromised patients from the general PACU population. It can be
equipped with an air-handling system that can be changed literally [4].
6.1.4 PACU Traffic

The orientation of the PACU should facilitate the flow of patients allowing direct
entrance to the PACU from an OR corridor and a preferably separate exit to a
main hospital corridor. Whereas, the use of the same PACU door for both
entrance and exit may inevitably lead to traffic jams and potentially dangerous
situations [4].
Both the entrance and exit doors must be extra wide to guarantee the passage
of a full-sized hospital bed with an ECMO/intra-aortic balloon pump console
and people pushing IV poles on both sides. The doors could be automatically
opened by a push button on the wall or by motion sensors [4].
It would be desirable to include a separate “pedestrian entrance” distinct
from the doors used for patient entrance and exit. This could facilitate movement
of staff and visitors and minimise distracting traffic jams, “whooshing” of the
doors and the introduction of contaminated air from other parts of the facility
[4].
6.1.5 PACU Bed-Spaces

It is a standard to budget a total of about 150–200 sq. ft. for each patient bed slot
separated with ceiling-to-floor privacy curtains between the bed-spaces to ensure
the patient privacy in the PACU as shown in Table 6.1 and Fig. 6.1c. Each bed
slot needs to be equipped with a pull-chain emergency call buzzer, allowing
patient to call the PACU nurse when step away from the side of the bed or
allowing the PACU nurse to call attention in emergency without yelling and
alarming other patients in the room [4].
Table 6.1 PACU bed-space
A floor space to the actual bed slot itself ≥100–120 sq. ft.
A working space to the nurses around all four sides of a bed ≥3 sq. ft.
A shelf space to supplies and equipment ≥12 sq. ft.
A writing surface nearby such as a rolling tray table
A floor space to IV poles or more convenient ceiling-track-mounted IV poles
Haret et al. [4]
6.1.6 General Considerations of the PACU

6.1.6.1 Layout
Two fire exits at opposite ends of the room are recommended in addition to
compliance with the institutional fire codes.
A nonslip tile floor in one neutral colour allowing finding dropped objects
(e.g. needle), and light, neutral, “warm” colours for the walls are usually
suggested (Fig. 6.5a).
Fig. 6.5 (a) A nonslip tile floor of the PACU and (b) a handwashing tool in the PACU
Multiple synchronised clocks to the same time should be readily visible

from all locations in the PACU.
A handwashing sink for each six bed slots is strongly recommended (Fig.
6.5b).
A medication room or area including a cabinet or carts is required (Fig.
6.4c).
Two separate utility rooms with storage areas should be incorporated into
the plan:
– The clean utility area includes a large blanket warmer (Fig. 6.4a).
– The dirty utility area should have three separate sinks for regular use,
instrument washing and flushing and a separate door to an outside
corridor, allowing removal of trash and contaminated waste and
dirty linen without carrying it past patients in the PACU.
Staff support space including:
– Adequate number of staff lavatories to the size of the staff, which
should be separate from any patient facilities.
– A staff break area is necessary and it could be equipped with a sleeve
patient’s monitor and alarms heard allowing continuous patient’s
observation while staff members are on break.
– An adequate desk space for physicians and staff to write notes or
dictate, including adequate number of terminals, if a computerised
information system is in use (Fig. 6.6a).
Fig. 6.6 (a) A PACU desk space for physicians and nursing staff to write notes, a
telephone line [A white arrow], a computer terminal and a central patients monitor and (b) a
bedside and (c) portable suction equipment
– Office space for the head nurse is a highly desirable addition (Fig.
6.6a).
6.1.6.2 Equipment and Drugs

The equipment and drug supplies should be stored and available in the
PACU, including suction equipment and oxygen supply sources at each bed
(Figs. 6.2, 6.4c and 6.6b, c).
A respiratory oxygen delivery system should be available for use in the
transport from the OR to the ward, to high-dependency area or the ICU.
6.1.6.3 PACU Lighting

It is desirable to have some daylight visible to patients in the PACU that has
the potential to reduce the postoperative cognitive dysfunction(POCD) [5].
Otherwise, the standard bright fluorescent lights are used in ceiling fixtures
(Fig. 6.1c).
Each bed-space needs enough levels of controllable lighting within the bed-
space.
A low-level night light is required for observation of a sleeping patient
when the unit is otherwise quiet to minimise the incidence of POCD [5].
In addition, the PACU should have at least one portable light that can be
moved to any bed slot to facilitate any needed procedures.
6.1.6.4 PACU Environment
(The average temperature in a PACU should be about 75 °F (24 °C) to
avoid aggravating OR- induced hypothermia, despite cooler temperatures,
may be favoured by the staff.)
The relative humidity should be maintained at 40–60 %.
The heating, ventilation and air conditioning system of the PACU should be
set to include a slight positive air pressure in the PACU, discouraging
entering bacteria from outside the PACU. There should be a minimum of
six air changes per hour, two of which are fresh outside air.
6.1.6.5 Electrical Power

At least six to eight regular outlets should be available on the head wall or
on the utility centre for each bed-space. At least two of them should be
clearly marked with red face plates and connected to an emergency power
system that has a kick-in time of <10 s following a power failure.
A supply of flashlights and battery-powered lanterns should be available to
avoid total darkness in the case of the power failure in which the emergency
power also fails.
Ventilators and infusion pumps for vasoactive drugs should always be
plugged into emergency outlets.
Additionally, several 240-volt plugs allowing the use of portable X-ray
machines should be available.
6.1.6.6 Medical Gases

The standard regulations for all medical gas installations must be
considered.
There should be at least two to three oxygen outlets (one having a flow
meter installed at all times) on the head wall or utility tree for each bed slot.
Three to five suction outlets should be available at the head of each bed slot
for tracheal suction, gastrointestinal suction, chest tubes, drains and airway
or surgical emergencies (Fig. 6.6b, c).
There should be one compressed air outlet at each bed-space to be used as a
blender for a ventilator.
6.1.6.7 Central Equipment in the PACU
One or more full resuscitation or “code” cart, including external and
internal defibrillating paddles, is needed for the thoracic patients depending
on the size of the unit (Fig. 6.3).
Both external and transvenous pacing electrodes and generators should be
available.
The difficult airway cart that should be kept in every PACU containing a
complete array of airway equipment, including a videolaryngoscope, a
fibre-optic bronchoscope and a light source.
A mechanical ventilator could be permanently kept in the PACU or to be
ready for rapid deployment when needed.
A number of surgical trays and supplies should be available at the PACU at
all times, including thoracostomy and tracheostomy trays and chest
reopening set because there is usually not enough time to have them
brought in from the OR in crisis cases.
6.1.6.8 Essential Equipment for Each Bed-Space

All stretchers used for patients in the PACU should be capable of a head-
down and semi-setting positions. Usually, having one stretcher per bed-
space is not enough, because it is unlikely the left stretcher with the
discharged patient to be returned in time to be ready for the next patient to
be transferred from the OR to that PACU bed-space.
A self-inflating resuscitator bag, a stethoscope and a warming device rather
than the traditional heated blankets should be available near the head of
each bed-space at all times.
Spirometers and negative inspiratory force meters must be enough so that
they are readily available when needed.
Other items that should be immediately at hand include a pressure bag for
rapid IV infusion, blood tubes, blood gas kits, basic nursing equipment (e.g.
emesis basin, gauze, gloves, eye protectors, pads, tape, IV equipment, etc.)
and tools (e.g. scissors, a clamp set, possibly a suture set, etc.).
6.1.6.9 Patient Monitoring

The recommended ASA standard monitors for all admitted PACU patients
include an electrocardiogram monitor, heart rate, a non-invasive blood
pressure module, a pulse oximeter, respiratory rate and a rapid-acting
electronic thermometer [6].
All of the PACU monitors should have invasive pressure channels for
patients undergoing thoracic procedures. Vital signs are recorded as often as
necessary but at least every 15 min while the patient is in the PACU.
At least one capnograph immediately should be available to monitor
ventilation in a seriously ill patient or verify correct tracheal intubation.
A dedicated cardiac output computer must be available if pulmonary artery
catheters are used.
There should be at least one peripheral nerve stimulator with TOF and
double-burst capability in the PACU to identify patients with PORC,
defined as a TOF ratio <0.9, which may occur in 22–60 % of patients in the
PACU.
Computerised patient data management systems have been widely used,
into which data can be entered by either direct capture of monitor signals or
entry by the PACU nurses or physicians.
6.1.6.10 PACU Communications

An inadequate number of telephones is a common problem in the PACUs.
Cordless telephones can be quite useful, since they allow the nurse to talk
on the telephone without leaving the bedside.
Of note, the main telephone at the PACU desk needs to be as free as
possible for incoming calls.
It is advisable to have a different telephone number from the main number
to be used only by the OR circulating nurses to inform the PACU about
impending patient transfers to the PACU.
A dedicated intercom system exclusive to the surgical suite area is a
potential alternative, which may or may not tie into the OR overhead
paging system.
Another option is to use two-way voice communication devices utilising the
hospital wireless network, voice recognition and wearable equipment
allowing the PACU nurse to continue taking care of the patient at the
bedside without a cordless phone.
More recently, a dedicated alarm system that would summon help in a crisis
(e.g. code situation) involving a large (often red) button under a clear
plastic cover at the desk or on the wall in a central location in the PACU is
considered to activate light and bell alarm in the OR and in the place most
likely to be populated by anaesthesia personnel who can respond
immediately.
6.1.7 Staff
Ideal staff should consist of:
An anaesthesiologist should be assigned to be responsible for final medical
decisions in the PACU (i.e. respiration, circulation, fluid, metabolic balance
and analgesia).
An expert charge nurse in the advanced cardiac life support directs the
PACU, acts as a backup care nurse when the PACU gets busy and
supervises the minute-to-minute operation [7].
Skilled PACU nurses trained in airway management, basic life support and
dealing with the unique patients emerging from anaesthesia after thoracic
procedures (e.g. caring for acute surgical wounds and a variety of chest
drains) should be capable to provide the direct early postoperative patient
care. Usually, it is necessary to have one PACU nurse caring exclusively for
each patient undergoing thoracic procedure, at least for the initial 15 min in
the PACU. After that, patients who are conscious and stable can usually be
monitored by a nurse who is simultaneously watching one similar patient.
Patients who are stable, awake, alert and uncomplicated who have been in
the PACU for more than 30 min can be watched even less closely. On
contrary, patients who are unstable or who have complications (e.g.
hypoventilation) require constant close monitoring regardless how long
they have been in the PACU [8]. Classically, the PACU nurses take at least
60 min to admit a patient, manage the patient’s recovery, get the patient
ready for discharge from the PACU and complete all the paperwork.
The operating surgeon is responsible for decisions about the results of the
performed thoracic procedure.
6.1.8 PACU Discharge Criteria

Discharge of patients after thoracic procedures from the PACU to the ward or
high-dependency unit is usually the responsibility of the physician or PACU
nurse according to the institutional policy and discharge criteria (Table 6.2) [4].
Brown et al. reported shortening the PACU stay by 24 % with using these
predetermined discharge criteria [11].
Table 6.2 Discharge criteria from the PACU to the ward
1. He/she is alert
2. Oriented to the time and place
3. Conversant and cooperative
4. If vital signs have been stable for at least 30 min
5. The patient could sit up without dizziness or nausea
6. The pain is considered tolerable, and the modified Aldrete score is ≥ 9 [10]
7. Outpatients should be discharged to a responsible adult who will accompany them home
8. Outpatients should be provided with written instructions regarding postoperative diet, medications,
activities and a phone number to call in case of emergency
Haret et al. [4, 9]
6.2 What to Treat in PACU?

There is an emphasis on the adverse events occurring in the PACU after thoracic
procedures such as airway obstruction, aspiration of vomitus and inadequate
ventilation from residual curarisation. Interdisciplinary rounds in the PACU can
potentially reduce these complications through improved quality of care and
effective communications between physicians, house and nursing staff [12].
6.2.1 Early Postoperative Complications

6.2.1.1 Postoperative Nausea and Vomiting (PONV)
The PONV has an overall 20–30 % incidence of patients undergoing general
anaesthesia. PONV has a significant negative effect on patient satisfaction with
anaesthesia, and even it may cause severe complications such as Boerhaave
syndrome, airway compromise and emphysema [13]. Independent predictors for
PONV include female gender, young age, non-smoking status, history of motion
sickness or past PONV, intraoperative using volatile anaesthetics or nitrous
oxide, prolonged duration of anaesthesia and postoperative use of opioids [13,
14]. Considering a multimodal approach can be effective for preventing PONV.
Many varieties of antiemetics could be used for treatment of the PONV as
shown in Table 6.3 and Fig. 6.7.
Table 6.3 Classes of commonly used antiemetics
Group Drug Adverse effects
1. 5-HT3 receptor antagonists Ondansetron Headache
Dolasetron Elevated transaminases
Palonosetron QT prolongation
Tropisetron Palonosetron shows fewer side effects
Granisetron
Palonosetron
2. Glucocorticoids Dexamethasone Hypotension
Increases blood sugar
3. Antihistamines Dimenhydrinate Drowsiness
Cyclizine Dry mouth
Tachycardia
QT prolongation
Visual disturbances
Dysuria
4. Cholinergic antagonists Scopolamine Visual disturbances
Dry mouth
Confusion
Hallucinations
5. Neurokinin-1 receptor antagonists Aprepitant Headache
(Off-label use) Fosaprepitant Elevated transaminases
Dry mouth
Drowsiness
6. Butyrophenone Droperidol QT prolongation
Haloperidol Hypotension
Reflexive tachycardia
Drowsiness
Dystonia
Anxiety
Agitation
Insomnia
Akathisia
Dyskinesia
Headache
Hypotension
Dry mouth
Visual disturbances
QT prolongation
7. Benzamide Metoclopramide Hypotension
Reflexive tachycardia
Dyskinesia
Modified from Haret et al. [4], Jokinen et al. [13]

Fig. 6.7 Approach for treatment of established PONV (Modified from Jokinen et al. [13], Haret et al. [4])
6.2.1.2 Postoperative Residual Curarisation (PORC)
PORC is commonly observed in the PACU when neuromuscular blocking drugs
are used intraoperatively. TOF ratios <0.70–0.90 are associated with upper
airway obstruction, inadequate recovery of pulmonary function, reduced
pharyngeal muscle coordination, an increased risk for aspiration and an impaired
hypoxic ventilatory response [15]. Conventional neuromuscular monitoring and
standard clinical tests (e.g. 5-s head lift) are unreliable in detecting PORC; thus,
incomplete neuromuscular recovery can be minimised with acceleromyographic
monitoring in the PACU [16].
6.2.1.3 Emergence Delirium and Postoperative

Dysfunction
Emergence from anaesthesia could be accompanied by signs of delirium,
including fluctuating mental status and inattention, with reported prevalence
rates of approximately 5–19 %[17]. Emergence delirium, primarily manifesting
with a hypoactive subtype, may be associated with prolonged PACU stays and
worse outcomes [18–20]. Preventable determinants for emergence delirium
include high postoperative pain scores, long fasting times, premedication with
benzodiazepines [17] and receiving opioids [18].
6.2.1.4 Anxiety in the PACU

Risk factors for postoperative anxiety in adults include the ASA physical status,
preoperative anxiety, minor psychiatric disorders, moderate to intense
postoperative pain and negative future perception. In contrast, the neural-block
anaesthesia, systemic multimodal analgesia and neuraxial opioids are protective
factors against postoperative anxiety [21]. Benzodiazepines in controlled
concentrations can be used to reduce postoperative anxiety even in elderly
patients. Of note, alternative therapies may include administering
dexmedetomidine or clonidine or considering acupressure, relaxation techniques
or massage therapy [22].
6.2.1.5 Glycaemic Control

Diabetes mellitus is the strongest risk factor for mortality following lung
transplant [hazard ratio 3.96 (2.85–5.51)] [23]. Hyperglycaemia as a result of
neuroendocrine and the stress response to surgical procedures is most notable in
the postoperative period in both diabetic and non-diabetic patients. Glycaemic
control in the postoperative period has been shown to reduce wound infections
and hyperglycaemia-associated poor outcomes [24]. Thus avoidance of severe
hyperglycaemia (>10 mmol/l (>180 mg/dl)) is important in adults after thoracic
surgery through continuous IV infusion of insulin in conjunction with glycaemic
monitoring every 30–60 min. Additionally, the preoperative ingestion of clear
fluids containing 50–100 g of carbohydrate until two hours before surgery,
unless contraindicated, and avoiding hypothermia and bleeding could minimise
postoperative insulin resistance [25]. Additionally, cautious should be exerted to
avoid hypoglycaemia during the postoperative period that may go unrecognised
and resulting in irreversible brain injury and mortality.
6.2.1.6 Pain in the PACU

Inadequate control of acute pain after thoracic surgery can potentially result in
postoperative pulmonary complications because of impaired sputum clearance
and reduced ventilatory capacity [26] or experiencing post-thoracic surgery
chronic pain [27].
A multimodal analgesia approach using different modalities with different
mechanism of actions such as regional (e.g. thoracic epidural analgesia (TEA),
paravertebral blockade (PVB), intercostal nerve block, intrapleural block,
cryoanalgesia, transcutaneous electrical nerve stimulation (TENS)) and systemic
analgesic techniques (e.g. opioids, ketamine, dexmedetomidine, clonidine, non-
steroidal antiinflammatory drugs (NSAIDs), paracetamol and local anaesthetic)
is commonly used for pain control in the PACU [28]. Of note, post-thoracic
surgery shoulder pain is usually refractory to TEA and requires NASIDs,
pregabalin and sometimes opioids [29, 30].
6.2.1.7 Hypothermia in the PACU

Inadvertent postoperative hypothermia is common among 60– 90 % of patients
in the PACU that could be associated with 300–400 % increase in oxygen
consumption.
It could result from the following:
Excessive heat loss due to exposure of the body surface to a low-
temperature environment, particularly during open thoracotomy and clam-
shell incisions
Affecting of normal thermoregulatory mechanisms secondary to the action
of general anaesthetic agents (e.g. intravenous and volatile anaesthetics,
muscle relaxants) or regional anaesthesia (e.g. TEA)
Several risk factors for postoperative hypothermia have been identified
including elderly, female gender, ASA physical status classes III or IV,
prolonged surgery >2 h, OR temperature <26 °C (78.8 °F), low body weight and
history of chronic endocrine diseases and intravenous infusion of cold fluids
[31].
Active warming, particularly forced air warming, is effective in treating
hypothermia [32]. Numerous drugs have been described to minimise
postoperative shivering such as clonidine, dexmedetomidine, meperidine,
nefopam, tramadol, ondansetron, granisetron and parecoxib [33, 34].
6.2.1.8 Postoperative Care of the Chest Drains

Chest tube suction appears to be superior to water seal in reducing the incidence
of pneumothorax [35].
Postoperative chest X-ray can be considered after thoracic surgery only if
complete expansion of the lung (pleurodesis, pneumothorax) is warranted [36].
Postoperative ultrasound may alleviate the need to perform routine chest X-rays
to rule out pneumothorax [37].
Bleeding after thoracic surgery occurs in <2 % of thoracoscopic procedures
and around 1 % to 3 % of open procedures because of surgical complications,
coagulopathy, receiving of antiplatelets or anticoagulants or certain
comorbidities (e.g. diabetes, renal or hepatic insufficiency) [38, 39].
Hourly observation of chest tube output with vital sign monitoring are
important to manage postoperative bleeding as follows [40]:
A chest tube output of 1000 ml in the first postoperative hour necessitates
an immediate re-exploration with concurrent correction of coagulopathy.
Drainage exceeding 200 ml per hour for 2 to 4 h after correction of a
coagulopathy also indicates surgical bleeding and dictates re-exploration.
If a patient is haemodynamically unstable but the chest tube output does not
suggest active haemorrhage, a chest radiograph is usually required to rule
out radio-opacity of the operative side with clotted chest tubes.
If a patient is haemodynamically stable but the chest output is high,
checking the haematocrit on the chest tube drainage can be helpful in
distinguishing active bleeding from a lymphatic leak.
The significant postoperative air leak after pulmonary resections can be
expiratory, forced expiratory, inspiratory (on positive pressure ventilation) or
continuous.
Management in the PACU [35]:
If there is no pleural space, then they are managed by underwater seal.
If there is a pleural space, negative suction is applied to the underwater seal.
6.2.1.9 Early Postoperative Hypoxemia and Oxygen

Therapy
Early tracheal extubation following thoracic procedures favours shorter stays in
the PACU and lower hospital costs [41]. The causes of postoperative
hypoxaemia (SpO2 <90 %, PaO2 <60 mmHg) are presented in Table 6.4 [42, 43].
Table 6.4 Causes of postoperative hypoxaemia
1. Inadequate pain relief

2. Hypothermia
3. Shivering
4. Hypoventilation
5. PORC
6. Use of opioids
7. Atelectasis
8. Pneumothorax
9. Post-pnuemonectomy or post-expansion pulmonary oedema
10. Activation of the inflammatory cascade
11. Excessive air leak
12. Aspiration of gastric contents
13. Excessive fluid therapy
14. Tachyarrhythmia (particularly AF)
15. RV dysfunction
16. Right-to-left shunt
17. Injury to the phrenic nerve
Intraoperative use of lung recruitment strategy, short-acting opioids and

neuromuscular blocking drugs, TEA or PVB and allowing patients to lay down
in the semi-setting position in conjunction with using supplemental oxygen in
the PACU can potentially prevent postoperative hypoxaemia [44–46]. NIV has
been established to treat postoperative pulmonary dysfunction to avoid re-
intubation in conscious patients with stable haemodynamics [47].
6.2.1.10 Cardiovascular Complications
They occur in 10–15 % of patients after major lung resection [48]. Most
important cardiovascular complications can be listed as arrhythmia, right-to-left
shunt, heart failure, cardiac herniation, cardiac tamponade and myocardial
ischaemia.
Postoperative SVT including AF is a common complication after pulmonary
resection, in 24–67 % of patients undergoing pneumonectomy and 12.3 % after
lobectomy. If patients have AF with compromised haemodynamic parameters,
then electrical cardioversion should be carried out immediately. If patients have
symptomatic AF, amiodarone could be used without increased incidence of
respiratory complications [49].
Heart failure occurs in 8.2 % after thoracic procedures [50]. In the PACU,
transthoracic echocardiography and functional class and N-terminal B-type
natriuretic peptide levels are parts of a multimodality approach to diagnose the
postoperative RV dysfunction [51, 52]. Pharmacological, ventilatory and
mechanical supports for the RV are used in order to optimise RV function by
controlling preload, decreasing afterload and providing inotropic support for
both ventricles.
Cardiac herniation is most commonly seen after pneumonectomy associated
with pericardiotomy or pericardiectomy [53].
Pericardial tamponade, though rare after open lobectomy, should be
considered along with other complications when a patient repeatedly develops
hypotension alongside an equalisation of CVP with pulmonary artery diastolic
pressure. Echocardiography is the diagnostic study of choice to visualise
impaired filling of the RV because of increased pericardial pressure.
Patients with significant coronary artery disease within 1 year of coronary
stenting pose high risks for postoperative myocardial ischaemia/infarction after
thoracic surgery [54, 55].
6.2.1.11 Fluid Therapy and Acute Kidney Injury

One of the independent risk factors for ALI after surgery for lung cancer is
excessive fluid infusion (odds ratio, 2.9; 95 % confidence interval, 1.9–7.4) [56].
IV fluids should be infused judiciously in the PACU at a recommended rate
of 1–2 ml/kg/h [57]. A fluid restriction after thoracic procedures could be guided
with using minimally invasive haemodynamic monitoring of pulse
pressure/stroke volume variation, extravascular lung water and intra-thoracic
blood volume index variables, but it is not clear whether the use of these
methods protects against development of postoperative AKI [58]. Decreased
urine output less than <0.5 mL/kg/h is a common occurrence in the PACU,
whereas AKI is uncommon in the PACU. Early postoperative AKI is associated
with more need for tracheal re-intubation, postoperative mechanical ventilation
and prolonged hospital stay.
Acknowledgements
The authors want to express his appreciation for Ms. Angelin Jeba Suja, PACU
staff nurse, King Fahd Hospital of the University of Dammam, for preparing the
included photographs in this chapter.
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DOI 10.1007/978-3-319-19908-5_7
7. Should I Blame the Surgeon: Surgical

Complications and Surgical Treatment of
the Complications
Jelena Grusina-Ujumaza1, 2 and Alper Toker2, 3
(1) Department of Thoracic Surgery, Pauls Stradins Clinical University
Hospital, Riga, Latvia
(2) Department of Thoracic Surgery, Group Florence Nightingale Hospitals,
Istanbul, Turkey
(3) Department of Thoracic Surgery, Istanbul University, Istanbul Faculty of
Medicine, Istanbul, Turkey

Alper Toker
Email: ae-toker@superonline.com
7.1 Introduction
In this chapter, authors try to clarify the postoperative major complications seen
after thoracic surgery, mainly after lung resections, mediastinal mass resections,
and lung transplantations. However this chapter did not deal with postoperative
arrhythmias and pulmonary edema, since they were discussed in other chapters
in this book.
7.2 Postoperative Hemorrhage and Residual Hemothorax

Chest tubes placed at the end of the operation help to prevent pneumothorax and
monitor air leaks and bleeding in early postoperative period. The incidence of
postoperative hemorrhage after thoracic surgery is variable and depends on the
type of operation: it can occur in 4 % of the cases after pulmonary resections and
just 0.33 % after mediastinoscopy [1, 2]. Most of the surgical bleedings (no
disorders of coagulation factors – normal INR (international normalized ratio),
prothrombin time, and thrombocyte count) are small in amount and generally
resolve spontaneously. Just a very few percent of bleeding (up to 2.6 %) needs
emergency surgery [3]. Criteria for postoperative bleeding control are the
amount of drainage and the hemodynamic effects of the drainage. A continuing
thoracic hemorrhagic drainage of more than 1000 ml or 200 ml/h for 4–6 h or a
sudden drainage of 400 ml may be a sign for a need of an emergency
intervention [4, 5]. A blood count should be obtained to detect any changes in
the hemoglobin and hematocrit levels, and a chest X-ray should be taken to
exclude hemothorax. Hematocrit of the blood obtained from chest tube may
indicate the severity of the drainage. If the hematocrit level of the chest drain
blood is more than 50 % of the blood hematocrit level, this may be a sign of
continuing hemorrhage. During early postoperative course, the thoracic drainage
system should be checked – it should be left open (except drainage after
pneumonectomy) and should work normal (we have to see oscillation in the
drainage tube). Following pneumonectomy, chest tube is recommended to keep
clamped and declamped for a few minutes in every hour to control the bleeding.
In an intubated patient, with a high positive end-expiratory pressure, the
presence of an air leak may be considered as normal. Also, a drain without any
oscillation may be normal in such patients.
Recently, due to increase of the patients with coronary artery stents, lung
resection candidates are more complicated because of perioperative
anticoagulation and antiplatelet therapy (APT). Bertolaccini et al. [6] found that
there were no statistically significant differences between the outcomes for the
38 patients receiving APT compared with the controls, in terms of the operative
time, the hospital stay, the estimated blood loss, or the morbidity when stratified
by the procedure [6]. On the other hand, in Foroulis’s study [7], it was shown
that APT use was a predisposing factor for postoperative bleeding.
In our experience, with increasing use of video-assisted surgery (VATS) and
vascular staplers, massive bleeding due to slipping of ligature is extremely
uncommon.
Residual hemothorax, which is not associated with an active bleeding, may
occur after thoracic surgery. Up to 15 % of the lung transplant recipients may
have this complication. Although thrombolytics may be recommended for a
successful treatment, authors prefer VATS for the evacuation of the retained
hemothorax [8]. In some patients, changing the location of the chest tube may
help in resolving of the residual hemothorax (Fig. 7.1).
Fig. 7.1 VATS for the evacuation of the retained hemothorax or revising the location of chest tube may
help in resolving of the residual hemothorax. (a) Early postoperative period. (b) Right sided hemothorax,
several hours later. (c) Residual hemothorax prior to indicated VATS evacuation. (d) One week after the
VATS with the upper displacement of the residual lung tissue
7.3 Cardiac Herniation and Tamponade

Cardiac herniation and tamponade are rare complications which may occur after
extended pulmonary resections – pneumonectomy or lobectomy – for malignant
diseases or pleuropneumonectomy for malignant mesothelioma or thymoma
surgery or when pericardiotomy or pericardiectomy is performed in addition to
any type of thoracic surgery. It may also occur after lung transplantation [9–11].
Cardiac herniation has a high mortality rate. Thirty to 50 % of cases may be fatal
because of a delay either in the diagnosis or the treatment. It is 100 % fatal, if
undetected [12].
The incidence of cardiac herniation after pulmonary resections for lung
cancer is about 1.7 % [13]. Cardiac herniation after right-sided pneumonectomy
is more frequent. It generally occurs in the first 3 postoperative days [14, 15]. It
presents with acute symptoms; there is a critical moment for cardiac herniation
and/or tamponade after pneumonectomy. It may occur even in the operation
room when patient is turned from the lateral decubitus to the supine position.
Acutely significant hypotension may present. The cause of this could be cardiac
strangulation (the size of the pericardial graft may be small), cardiac herniation
(after pericardiectomy without the closure of the pericardium or patch
dehiscence), or tamponade. Transesophageal echocardiography can assist in
decision-making before leaving the operating room without reopening the
thoracotomy [9]. During the early postoperative period, risk factors for a cardiac
herniation could be increased due to the increased intrathoracic pressure with
cough and sputum expectoration, the positive-pressure ventilation, the negative
suction from drain, and the changes in patient’s position (e.g., lying on the side
of surgery) [5]. Symptoms start suddenly with the presentation of superior vena
cava syndrome, low cardiac output, dysrhythmias, hypotension, cardiac arrest,
and shock. For diagnosis, chest X-ray (shadows of the heart and apex),
electrocardiography (ECG), and echocardiogram have to be performed for the
diagnosis. The clues of the herniation include axis change on ECG, cardiac
malrotation on echocardiogram, and hemodynamic collapse [16]. Thorax
computed tomography (CT) (if hemodynamics of patient allows) is also
recommended. Treatment should be started immediately – the patient should lie
opposite to the surgical side and emergency reoperation has to be performed.
Cardiac tamponade as a complication after extrapleural pneumonectomy may
occur in 3.6 % of the patients [9]. Postoperative bleeding into the pericardial sac
may occur even after lobectomy without pericardiectomy. The patient may have
acute clinical presentation and needs an urgent surgery [17]. It was proposed that
an intrapericardial retraction of the suture line of the divided pulmonary vein
could cause a bleeding from the malfunctioning staple line, and this could lead to
a cardiac tamponade [18–20]. It can be treated just with a transcutaneous
pericardial drainage and/or immediate surgery.
Cardiac tamponade is characterized by a low cardiac output and a classical
Beck’s triad (hypotension, muffled heart sounds, and distended neck veins). The
chest X-ray, ECG, and echocardiogram should be performed. Surgical treatment
is recommended in most of the cases.
These complications might be the cause of cardiac arrest and could have fatal
results. Sugarbaker [9] wrote that a cardiac arrest within 10 days postoperatively
needs emergency thoracotomy (sometimes in the intensive care unit), open
cardiac massage, and pericardial patch removal. Closed cardiac massage is not
effective enough after pneumonectomy, since the heart has shifted out of the
midline, and it cannot be properly compressed by the sternum and vertebral
column. All the members of the postoperative care team must be educated on
this point to avoid losing valuable time performing futile closed-chest
compressions [9].
7.4 Lobar torsion and gangrene

Lobar, segmental or common basal pyramid torsion is a rare complication which
may occur after different type of pulmonary resections and lung transplantation
with an incidence rate less than 0.1% [21–23]. Usually torsion occurs in the
middle lobe or in the left lower lobe following upper lobe resections.Lobar
torsion may develop in the first postoperative 2 weeks [21, 23, 24]. The rotation
of the bronchovascular pedicle results with bronchial obstruction and vascular
compromise is the cause of gangrene and potential mortality if left untreated
[25]. Recognition of pulmonary torsion may be difficult. Clinical presentations
vary from slight hypoxemia to septic shock. The clinical findings depend on the
degree of rotation in the lobar hilum, generally the rotation is 180 degrees
although 90 and 360 degree torsions have been reported [26].Symptoms of
pulmonary torsion can start suddenly with an unexplained dyspnea, productive
cough, hemoptysis, tachycardia, and fever, diminished breathing sounds on the
effected side or presence of air leak.Chest radiographs may show opacification
of the lobe. Findings do not change after nasotracheal aspiration.Chest X ray
may demonstrate pneumothorax or collapsed lobe in an unusual position. High
resolution chest computed tomography with pulmonary angiogram may confirm
the diagnosis - opacification, complete obstruction –“cut-off’’- of the bronchus,
stenosis or obstruction of kinking vessels are the radiological findings [23].
Flexible bronchoscopy should be performed and diagnosis may be confirmed if
“fish mouth’’ like appearance is noticed.The transesophageal echocardiography
may reveal a presence of potential lethal thrombus in pulmonary vein. Urgent
reoperation is indicated, reposition and fixation with following anticoagulant
therapy to or complete resection could be performed, if pulmonary infarction or
gangrene is suspected.Good analgesia, aggressive antibiotics treatment and mini-
tracheostomy to aid suctioning of the secretions may help to reduce the
infectious complications after torsion [25].
7.5 Air Leak and Subcutaneous Emphysema

An air leak after pulmonary resection is the most commonly seen finding. In the
early postoperative period, it may be seen at a rate of 28–60 % of the patients;
however, in the immediate postoperative period, an air leak should not be
considered as a pathological condition. A pathological “air leak” may refer to
any leakage of the air from the lung identified by noting bubbles in a chest
drainage system, by progressive subcutaneous emphysema, or by expanding
pneumothorax [27, 28]. On the morning of the postoperative day (POD) 1, an air
leak is present in 26–48 % of the patients, with a decreasing incidence toward
the POD 4 to as low as 8 % [29–31]. But, in some specific procedures such as
bilateral lung volume reduction surgery, an air leak may occur in 90 % of the
patients [32]. If an air leak is longer than 7 days (some consider more than 4
days and more than 10 days), it may be considered as prolonged air leak (PAL)
[27]. The incidence of PAL is between 9.6 and 15 %, and also it was suggested
that PAL may increase the rate of other pulmonary complications, including
atelectasis, pneumonia, and empyema, but it is not associated with an increased
incidence of cardiopulmonary morbidity [31, 34]. As a result of PAL, the
postoperative length of stay is increased [28, 35]. An empyema can develop in
11 % of the patients with PAL [31]. Among the most important risk factors of
PAL are an underlying COPD, an inhaled steroid treatment, an active pulmonary
infection, insulin-dependent diabetes, a low body mass index (<25.5 kg/m2), a
reduced forced expiratory volume in the first second (FEV1) or reduced
predicted postoperative FEV1, an upper lung field resection, lung volume
reduction surgery, and intraoperative pleural adhesions [32, 36]. As previously
mentioned, chest tube drainage systems may help to monitor the air leak after
pulmonary surgery. Different chest tube modalities can be used in postoperative
period – water seal or negative pressure drainage system −20 cm H2O or −10 cm
H2O suction. Chest tubes placed on water seal after pulmonary lobectomy are
generally well tolerated and safe; however, they do not reduce the duration of the
air leak or the incidence of prolonged air leak when compared with negative
suction tubes [33]. Air leak volume can be seen easily, if digital drainage system
is used. If a high volume of air leak persists, a pneumothorax and/or
subcutaneous emphysema may develop, and negative pressure drainage system
should be used in this situation. Chest tube can be removed, if there is no air leak
and drainage is less than 200 ml in the last 24 h, but generally drainage volume
depends on the underlying disease and the surgery performed. For instance, in
our practice we remove chest tube, when there is no drainage and air leak after
radical pleurectomy and decortication surgery for mesothelioma. We may
remove chest tubes when the daily drainage is around 400 ml or the drainage is
less than 50 ml in the past 12 h in conventional lung resections like a lobectomy.
If there is a small air leak and the lungs are totally expanded, the chest tube
may be clamped (which is named as “provocative clamping”), and a chest X-ray
should be taken to determine whether the lung remains expanded or not. The
tube can be removed if the lung remains expanded, but if the lung collapses and
subcutaneous emphysema develops, then the clamp should be opened and the
patient can be discharged with a Heimlich valve connected to chest tube.
Operation for PAL is rarely necessary. Sometimes talc pleurodesis or an
autologous blood patch via chest tube can be tried, or an endobronchial valve
may effectively solve this problem especially in high-risk patients [29, 37, 38].
Subcutaneous emphysema (SE) as a complication of air leak may occur
when air enters into the subcutaneous space of the chest wall and the soft tissues
of the face, neck, upper chest, and shoulder and may change voice. SE could
expand to the abdomen subcutaneous space or even into the peritoneum.
Cerfolio [30] reported that SE occurs in 6.3 % of the patients after pulmonary
resections. Although nonlethal, it may be difficult to convince the family
members and other colleagues from the intensive care unit. A CT scan to identify
an air pocket and to guide additional percutaneous drainage catheters may be
helpful. Bronchoscopy may be required to exclude a bronchopleural fistula or a
possible tracheal laceration during the intubation. Depending on the severity of
SE, there are different methods of management, including observation,
reoperation, and usage of pop-off valves. If reoperation is necessary, VATS or
thoracotomy can be performed [30].
7.6 Chylothorax
A chylothorax is a leak of lymphatic fluid with chylomicrons and fats into the
thoracic cavity. Chylothorax could be observed as milky or creamy pleural
effusion coming from the chest tube in the early postoperative period or several
days after surgery. It may occur as a result of a laceration of lateral branches of
the lymphatic duct or direct iatrogenic duct injury and/or incomplete ligation of
the lymphatic duct during some procedures, among which are extended
mediastinal lymph node dissection, mediastinal tumor resection, esophageal
resection, or extrapleural pneumonectomy [39]. The incidence after pulmonary
resection is between 0.2 and 2.1 % and after esophagectomy 3.8 %, and the
incidence rate also depends on the preference of mediastinal lymph node
dissection techniques [39–43]. The diagnosis of a chylothorax is established if
pleural effusion has a high level of triglyceride (>110 mg/dL), but if the level is
between 50 and 100 mg/dL, lipoprotein analysis should be performed [41]. If
triglyceride concentration is lower than 50, it is probably not a chylothorax. A
persistent leakage may lead to albumin and antibody loss, malnutrition, and
lymphocytopenia and increase the risk of bacterial and viral infections which is
associated with significant postoperative morbidity and mortality [43]. In
addition, an average daily chest tube output exceeding 400 mL in the early
postoperative period should prompt fluid analysis for chylothorax to facilitate
early diagnosis and consideration of thoracic duct ligation [43]. The first choice
in the treatment is to stop oral diet intake and immediately to start parenteral
feeding. Daily drainage volume has been controlled, and decision whether to
continue conservative treatment or to perform surgery has been made. Most of
the postoperative chylothorax may be resolved by conservative therapy
including octreotide/somatostatin infusion [42, 44, 45]. If the amount of the leak
is low, it could stop at seal on its own, but before removing the chest tube, the
patient should be given a fatty meal diet for two days, and if output is still
nonchylous and the volume is low, then the chest tube is removed [40]. But if
chylous leakage is greater than 2000 ml for the first 2 days, or as suggested by
some authors greater than 1000 ml/per day for 5 days, reoperation should be
performed without waiting any further [46, 47]. Lymphangiography and
lymphoscintigraphy are useful to localize the leak [44, 45]. The alternative
method of the management of the chylothorax is percutaneous catheterization of
the thoracic duct and embolization [48].
7.7 Nerve Injury

Extended thoracic surgery may cause intrathoracic nerve injury (phrenic or
recurrent laryngeal nerves). Most of the phrenic nerve injuries in literature are
described after cardiac surgery, but it may also develop after thoracic surgery
such as extended pulmonary resection, esophageal or mediastinal surgery, and
cervical rib resection for thoracic outlet syndrome [49]. It may present with
unilateral or bilateral diaphragm palsy and results in atelectasis, pneumonia,
decreased pulmonary function, sleep-disordered breathing, and pulmonary
effusion. It usually can be suspected when patient has decreased exercise
tolerance or dyspnea. An intubated patient may have difficulties in weaning. X-
ray demonstrates elevation of the affected hemidiaphragm, and ultrasound
examination confirms the diagnosis [50]. The best treatment of choice is surgery,
either diaphragmatic plication or phrenic nerve reconstruction for unilateral
injury or diaphragmatic pacemakers in cases of bilateral injury [50–54]. In Fig.
7.2, you may see a patient with phrenic nerve paralysis and chest X-ray after
VATS plication.
Fig. 7.2 (a) Chest X-ray view of a patient with phrenic nerve paralysis. (b) Chest X-ray view of a patient
after VATS diaphragmatic plication
The recurrent laryngeal nerve has a high risk of injury during the dissection
of the subaortic region, especially during pneumonectomy and esophagectomy,
or in cases where patients received preoperative radiotherapy [55]. Recurrent
laryngeal nerve palsy after mediastinal lymph node dissection may occur in up to
1.5 % and after esophagectomy up to 8 % but after left-sided pneumonectomy up
to 30 % of cases [56–58]. The result of the injury is vocal cord paralysis, which
is suspected if the patient has a weak or whispery voice or a weak cough or if the
patient aspirates after water intake in early postoperative period; the last
symptom should be differentiated from vocal cord edema in the very early
postextubation period. When vocal cord paralysis is suspected, laryngoscopy or
flexible fiber-optic laryngoscopy should be performed and followed by
laryngostroboscopy and laryngeal electromyography. The management involves
pulmonary physiotherapy to decrease risk of aspiration, medialization
laryngoplasty with or without implant material, or injection medialization
[59–61]. Bilateral vocal cord paralysis is a catastrophe, which may occur after
tracheal stenosis resection at the subglottic level. Experienced tracheal surgeons
know the pitfalls and generally never have this complication.
7.8 Right-to-Left Shunt

Right-to-left shunt or platypnea-orthodeoxia syndrome is rarely observed after
right-sided pneumonectomy operation or after an elevated right hemidiaphragm.
The presence of a persistent foramen ovale (PFO) or open atrial septal defect can
cause this syndrome. It is diagnosed by echocardiography or MRI. PFO is found
in about 20 % of the normal population. Patients with PFO after
pneumonectomy may not suffer from dyspnea and desaturation in supine
position, but they may occur in sitting or upright position. Though PFO is
normally asymptomatic, it is a potential source for a right-to-left shunt when the
pulmonary artery and right heart pressure are increased [62–66].
Perkins [63] recommended including cardiac shunt in the differential
diagnosis of hypoxemia, even in the presence of normal cardiac pressures, once
other more common causes have been excluded. Transesophageal
echocardiography may confirm the diagnosis. If the shunt persists, it needs
percutaneous or surgical closure.
7.9 Atelectasis
Atelectasis is the collapse or incomplete expansion of the lung or part of the
lung. It is one of the commonest abnormalities in chest X-ray after thoracic
surgery, and it may be life threatening if not treated correctly. Atelectasis can
occur in 15 % of the patients, and it is seen more frequently following right
upper pulmonary resections [1, 67]. The cessation of smoking before surgery and
preoperative bronchodilators can help to prevent atelectasis. Predisposing factors
for atelectasis after surgery are secretion retention, hypoventilation, pulmonary
edema due to volume overload, decreased ciliary activity after sleeve resection,
and COPD. Symptoms of the atelectasis are dyspnea, tachypnea, decreased
respiratory sounds, tachycardia, and fever. Defined opacity, volume loss, fissure
displacement, heightened hemidiaphragm, and mediastinal shift can be seen on a
chest radiograph. Early pulmonary physiotherapy and nasotracheal aspiration are
usually helpful in the postoperative period. Endobronchial aspiration and lavage
with bronchoscopy may be performed (Fig. 7.3). The Thoracic Surgery Database
had informed that about 3.7 % of atelectasis cases require bronchoscopy after
lobectomy. Another helpful technique may be noninvasive positive-pressure
ventilation and also effective pain management [5, 68, 69].
Fig. 7.3 Early pulmonary physiotherapy and nasotracheal aspiration are usually helpful in the prevention
of postoperative atelectasis. Endobronchial aspiration and lavage with bronchoscopy help in the treatment
of atelectasis. (a) Right lung atelectasis. (b) Immediately after the nasotracheal suction. (c) The next day
with aggressive physiotherapy
7.10 Postsurgical Empyema

Postsurgical empyema is the development of infection in the pleural space after
esophageal, pulmonary, or mediastinal surgery. The incidence is higher in
pneumonectomy (2–12 %) and may occur in 3 % of patients after lobectomy; the
majority of these patients also present with a bronchopleural fistula (BPF) [5].
The incidence of the postsurgical empyema increases according to the indication
of resection – inflammatory or neoplastic disease and the presence of a
neoadjuvant therapy [70]. Risk factors include older age, cardiopulmonary
impairment, malnutrition, induction therapy (especially chemoradiotherapy),
diabetes, steroids, right-sided pneumonectomy, extended resections,
postoperative pneumonia, and prolonged mechanical ventilation giving rise to
barotrauma. Empyema can occur secondary to a spontaneous pneumothorax with
persistent bronchopleural fistula [71]. PAL increases the risk of empyema up to
11 % [11]. Most of the cases develop in the early postoperative period (generally
in first 3 months) but may occur also later (Fig. 7.4). The contamination of the
pleural space develops from a BPF or esophagopleural fistula or from blood-
borne sources. Clinical symptoms are mostly age specific and related to the
general condition of the patient. The patient may be asymptomatic but may also
have fever, fatigue, chest pain, dyspnea, and purulent or serosanguinous
expectoration. The first sign of empyema is a change in the drainage pattern
from serous to purulent, if the chest tube is still in place. And if it continues with
air leak, the diagnosis of the BPF can be suspected. A pleural opacity with or
without fluid level is usually detected on postoperative chest X-ray after
lobectomy or segmentectomy. But after pneumonectomy, a decrease in the fluid
level is visible. The most common bacterial pathogens are Staphylococcus,
Pseudomonas, and anaerobic microorganisms. The treatment of the pleural
empyema depends on the time of the diagnosis and the presence of the BPF and
patients’ general condition. The management includes antibiotic therapy and
adequate chest tube thoracostomy with sensitive antibiotic solution irrigation to
clean the remaining cavity [71]. After patient is stabilized (usually in 1–2
weeks), surgery may be performed. For empyema treatment, surgeon may
perform Eloesser procedure, myoplasty with muscle flap closure, thoracoplasty,
or modified Clagett or Eloesser procedure [72].
Fig. 7.4 CT scan view of a patient with empyema after lung resection (a–b)
7.11 Bronchopleural Fistula

BPF is a connection between the bronchus and pleural space. BPF ranges from
small to large, the latter being a nightmare for thoracic surgeons often leading to
life-threatening events. This complication leads to an increased morbidity and
mortality after pulmonary resection. The overall incidence is 4.4 %, and it
depends on the resection type [73]. Mortality rate is between 40 and 70 % of the
patients with BPF after pulmonary resection [74, 75]. Risk factors of BPF
include right-sided or completion pneumonectomy, surgery for infectious or
inflammatory diseases, high-dose induction radiotherapy, prolonged mechanical
ventilation, empyema, infected postresectional space, and residual tumor at the
bronchial stump (Fig. 7.5). Most deaths are due to sepsis facilitated by aspiration
pneumonia, ARDS, and malnutrition. Massive hemoptysis may be seen very
rarely as a result of pulmonary artery erosion due to an infective inflammation.
Most frequently a BPF is seen in 1 week after surgery [71, 72].
Fig. 7.5 Risk factors of bronchopleural fistula include right-sided or completion pneumonectomy, surgery
for infectious or inflammatory diseases, high-dose induction radiotherapy, prolonged mechanical
ventilation, empyema, infected postresectional space, and residual tumor at the bronchial stump.
Bronchoscopic demonstration is the key to a definitive diagnosis
Small fistulas may be asymptomatic and close without any special treatment,
but some BPF can lead to tension pneumothorax, aspiration pneumonia, and
asphyxia. It can start with sudden dyspnea, excessive coughing, fever, fatigue,
bloody sputum, and subcutaneous emphysema. In the case of tension
pneumothorax, emergency chest tube drainage should be performed. If there is a
suspicion of a BPF after pneumonectomy, the patient should be laid down on the
operation side for protection of the opposite lung from contamination, and
adequate chest drainage and antibacterial treatment should be performed [72].
Bronchoscopy is useful to confirm the diagnosis by demonstrating the presence
of the BPF (Fig. 7.5). If there is no visible fistula and the suspicion continues,
methylene blue injection to the bronchial stump may be performed; the drainage
of the methylene blue via the chest tube is then diagnostic. During
bronchoscopy, a balloon catheter may be inserted to see whether it stops the air
leak. There is a typical decrease in the fluid level on the operated side after
pneumonectomy. Also ventilation scintigraphy with inhalation of a radionuclide
can be helpful for diagnosis. The definitive treatment should be chosen
according to a diameter of the fistula and general conditions of the patient. The
repair of the bronchial stump may be considered in pneumonectomy patients
with early BPF (i.e., within 2 weeks). Open-window thoracoscopy can be
performed for BPF with empyema treatment [71, 72].
7.12 Complications After Lung Transplantation

7.12.1 Vascular Anastomotic Complications
Complications of the arterial and venous anastomoses include stenosis, arterial
kinking, and thrombus formation. Pulmonary artery stenosis has been reported in
the early and late period after lung transplantation. There may be dyspnea, signs
of pulmonary hypertension, and right heart failure (e.g., systemic hypotension,
peripheral edema). Echocardiography may demonstrate an increased right
ventricular pressure or right ventricular dysfunction. Quantitative
ventilation/perfusion scan shows unequally distributed blood flow between the
lungs after bilateral transplantation or disproportionate flow to the native lung
after single-lung transplantation. Pulmonary angiography is usually necessary to
confirm the diagnosis and helps in balloon dilatation or stent placement. Surgical
reconstruction is the final option for stenosis not amenable to other interventions
[73–77].
Kinking of the pulmonary artery is associated with decreased flow in the
pulmonary vein, as assessed by transesophageal echocardiography [78].
Percutaneous placement of a metallic stent is recommended.
Pulmonary vein thrombosis occurs in the early postoperative period.
Thrombus formation at the pulmonary venous/left atrial anastomotic suture line
carries the risk of systemic embolization and cerebrovascular accident, and also
it may obstruct pulmonary venous outflow and cause severe pulmonary edema
refractory to medical management [79–81].
Clinical features include hypoxemia, decreased lung compliance, and diffuse
radiographic opacities in the allograft. The diagnosis is made by transesophageal
echocardiography.
There is no standardized management of the pulmonary vein thrombosis
after lung transplantation. Fibrinolytic therapy can be useful, if the bleeding risk
is not high [82]. Refractory hypoxemia and/or hemodynamic instability may
require emergent surgical thrombectomy, but outcomes are usually poor. On the
other hand, small venous anastomotic thrombi can resolve spontaneously [5, 83,
84].
7.12.2 Airway Complications

With the improvements in the surgical techniques and perioperative management
of lung transplantation, the incidence of airway complications (AC) decreased to
10–20 % with a related mortality rate at 2–3 % [85–87]. Several risk factors for
AC were identified: surgical technique, infections, and several
immunosuppressive medications. The current recommendations are to avoid
sirolimus at least 90 days after transplantation because of its antiproliferative
properties. Donor and recipient risk factors could cause AC such as duration of
donor’s mechanical ventilation (50–70 h before organ retrieval) or difference
between donor and recipient’s bronchial diameters. Other risk factors may be
primary graft dysfunction, acute cellular rejection, positive-pressure mechanical
ventilation and need for a high positive end-expiratory pressure (PEEP), organ
preservation technique, acute kidney injury, etc. Primary graft dysfunction,
which is a type of reperfusion injury, may compromise pulmonary flow and
increase the length of mechanical ventilation, and the high level of PEEP may be
required. Positive-pressure mechanical ventilation and PEEP have a potential to
increase the bronchial wall, and anastomosis stress and graft perfusion might be
impaired when high inflation pressures are needed [88–92].
Bronchial stenosis is one of the common complications with a reported
incidence between 6 and 23 % [93, 94]. It may be asymptomatic and diagnosed
by routine bronchoscopy or may have a slight clinical symptom or manifestation
of bronchial stenosis more frequently with increasing dyspnea, cough, post-
obstructive pneumonia, or radiographic abnormalities. Bronchoscopy is a
standard method for diagnosis. Management of bronchial stenosis includes
balloon dilatation, ablation with cryotherapy, electrocautery or laser argon
plasma coagulation, and stent placement [92, 95, 96].
7.12.3 Necrosis and Dehiscence

Isolated necrotic changes of the anastomosis may develop in patients undergoing
transplantation, between first and fifth weeks. Necrosis can resolve quickly or
can progress to the dehiscence. Early diagnosis is important. And if there is
clinical presentation of prolonged air leak, pneumothorax, or
pneumomediastinum, there exists the possibility of anastomosis dehiscence
being a suspect too. Flexible bronchoscopy is a gold standard for diagnosis, and
view of significant necrosis and loose sutures may be seen. Management of
anastomotic dehiscence is surgical repair or even retransplantation [97].
Airway fistulas after lung transplantation are uncommon. Fistulas have been
described between the airway and the pleura, mediastinum, aorta, pulmonary
arteries, and left atrium. BPF is rare and may present with dyspnea, hypotension,
sepsis, pneumothorax, subcutaneous emphysema, or persistent air leak.
Endoscopic techniques for closing of fistula or surgical options can be used.
Bronchomediastinal fistula has a high mortality, and the clinical presentation can
be bacteremia, sepsis, mediastinitis, mediastinal abscess, or cavitation. Surgical
treatment is recommended. Bronchovascular fistulas can present with minimal
hemoptysis to fatal bleeding. These complications are rare but associated with
high mortality. It should be suspected at the case of Aspergillus infection [97].
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DOI 10.1007/978-3-319-19908-5_8
8. Should Every “Myasthenic

Thymectomy” Be Sent to ICU?
Zerrin Sungur1 and Mert Şentürk1
(1) Department of Anesthesiology and Intensive Care Medicine, Istanbul
University, Istanbul Faculty of Medicine, Istanbul, Turkey

Zerrin Sungur
Email: zerrin_sr@yahoo.com
8.1 Introduction
In recent years, perioperative approach to patients with myasthenia gravis (MG)
has changed substantially as a result of new information obtained about its
pathology and improved the therapeutic solutions. Regarding surgical treatment,
not only the experience has improved but also new minimally invasive
techniques such as “video-assisted thoracoscopic extended thymectomy
(VATET)” are associated with a better outcome and decreased incidence of
catastrophic complications [1]. Last but not the least, regarding anesthetic
approach, new drugs in our armory have challenged the classical encountered
problems. Nonetheless, safe and effective treatment of a myasthenic patient in
the perioperative period remains multidisciplinary. This review will focus on
general information of MG and possible postoperative challenges.
8.2 General Information

Myasthenia gravis (MG) has first been described at the end of the nineteenth
century as a progressive decline in the tension of simulated muscles which
resolves at rest. Later in the twentieth century, it is called as an autoimmune
disease affecting postsynaptic membrane in adulthood. The pediatric or juvenile
form of the disease was defined later in the middle of the twentieth century. The
term “juvenile MG” (JMG) is currently used for patients between 0 and 19 years
old [2]. However this definition excludes neonatal MG which is caused by
passive transfer of maternal AChR antibodies. In neonatal MG, muscle weakness
is relieved in 2–4 weeks, and therapy remains mostly symptomatic.
Possibly due to better diagnosis and treatment approaches in the last decades,
prevalence and incidence of MG appears to be increased [3]: The pooled
incidence rate is reported to be about 5.3 per million person-years and the
estimated pooled prevalence rate about 77.7 per million. For JMG, the incidence
in Europe is reported to be 0.1–0.5/100.000 per year [4, 5].
MG is caused by pathogenic autoantibodies to components of the
postsynaptic muscle end plate. A subgrouping based on the different antibodies
has been defined recently [6]. This classification affects also the clinical
approach, including surgery. Briefly, there are autoantibodies against the
acetylcholine receptor (AChR), muscle-specific kinase (MuSK), and lipoprotein-
related protein 4 (LRP4). MG with AChR antibodies is further divided to “early-
onset” and “late-onset” MG. Moreover, “thymoma-associated,” “antibody-
negative generalized,” and “ocular” types are also differentiated. Among them,
“early-onset MG with AChR antibodies” and “thymoma-associated MG” can
profit from surgical treatment. Generally, there is a close relationship between
the indication for surgery and cellular abnormalities of thymic gland
(hyperplasia or thymoma). JMG is often seropositive with anti-AChR [6].
8.3 Diagnosis
Initially, clinical suspicion of fluctuating muscle weakness leads to further tests
of definitional diagnosis, which consists of three tests [7]:
1. Edrophonium test: Edrophonium is a short-acting anticholinesterase (anti-

AChE) drug. The test is accepted as positive if patient’s muscle weakness is
ameliorated 45 s after drug administration and this improvement continues
approximately for 5 min.
2. Electromyography: A decremented response of affected muscles for

repetitive action potential is a characteristic finding of MG for EMG studies.
These findings may also be seen in similar disorders such as Lambert-Eaton
syndrome and certain myotonies or motor neuron diseases.
3. Detection of antibodies: The presence of anti-AChR antibodies is
pathognomic for MG.
8.4 Clinical Course

Muscle weakness, which is the main feature of disorder, improves at rest and
worsens with activity [8]. Therefore, a myasthenic patient who is not undergoing
surgery may also require mechanical ventilation support during any exacerbation
of the disease.
The common peak for age onset is at third decade and mainly in women; a
secondary peak is also reported in older men after fifth decade.
More than half of subjects have ocular signs like diplopia or ptosis.
Extremity muscles are affected in such a way that results in fatigue more
prominently at the end of day. In the limbs, proximal muscle groups are more
frequently impaired than distal muscle groups. Patients may also present with
dysphagia or dysarthria together with bulbar impairment which is an indication
of a more severe disease. In such cases, possibility of aspiration or malnutrition
should be investigated preoperatively. Table 8.1 summarizes clinical
classification originally suggested by Osserman and later modified by the
Myasthenia Gravis Foundation of America.
Table 8.1 Myasthenia Gravis Foundation of America Clinical Classification
Stage Clinical status
I Only ocular involvement
II Generalized mild muscle weakness
IIa Predominantly affects limb and axial muscles
IIb Predominantly bulbar involvement or respiratory weakness
III Generalized moderate muscle weakness
IIIa Predominantly affects limb and axial muscles
IIIb Predominantly bulbar involvement or respiratory weakness
IV Generalized severe muscle weakness
IVa Predominantly affects limb and axial muscles
IVb Predominantly bulbar involvement or respiratory weakness
V Tracheal intubation or mechanical ventilation
MGFA Myasthenia Gravis Foundation of America
8.4.1 Comorbidities and Drug Interactions

Any patient with MG should be investigated for other autoimmune diseases such
as endocrine diseases (thyroid disorders), rheumatoid arthritis, ulcerative colitis,
and sarcoidosis, as these disorders are frequently encountered [9]. As previously
mentioned, malnutrition due to dysphasia or hypothyroidism as a result of
autoimmune disease requires extra attention from the anesthesiologist as they
may affect postoperative recovery. If detected, these conditions must be treated
prior to surgery.
Several conditions that may exacerbate the course of disease and may even
cause the need for mechanical ventilation are reported. Infections, thyroid
disorders, radiation, and extreme temperature are frequent pathological risk
factors; however, sleep disorders, pain, or menses may also worsen patient’s
status [6, 9]. Besides drugs which may affect/weaken neuromuscular junction, a
large variety may aggravate the course of the disease in a dose-dependent
manner with antibiotic [e.g., aminoglycosides], antiarrhythmic [e.g., verapamil],
and neuropsychiatric agents (Table 8.2). Although corticosteroid is a part of the
therapy, it may paradoxically cause an early exacerbation of MG. If surgery
should be performed at initial phase of steroid therapy, anesthetist must be aware
of this worsening effect [10].
Table 8.2 Myasthenia gravis drug medication list (MGFA)
Group Risk Drug Comments
Antibiotics
Aminoglycosides 2 Gentamicin, amikacin, Eye preparation can exacerbate ocular
tobramycin, neomycin, myasthenia
streptomycin
Ketolide 1
Glycopeptides 2 Telithromycin
Lincosamide 2 Vancomycin
Fluoroquinolones 3 Clindamycin Eye preparation generally safe
Ciprofloxacin, levofloxacin, etc.
Penicillins 4 Ampicillin, amoxicillin, Little evidence of causing problem
penicillin G, etc.
Cardiac medications
Class I 2 Procainamide, quinidine, Avoid use if possible; can be used if
antiarrhythmics lidocaine, etc. arrhythmia is emergent and there’s no
alternative
Beta-blockers 3
Calcium canal Atenolol, labetalol, metoprolol, Oral, parenteral, and ophthalmic preparations
blockers etc.
Statins 3 Verapamil, diltiazem, nifedipine, Verapamil is the worst; all should be used with
etc. caution
Atorvastatin, simvastatin
Antiepileptics
Hydantoin 3 Phenytoin
Barbiturate 3 Phenobarbital, pentobarbital,
etc.
Other 3 Gabapentin
Psychiatric medications
Antimanic 3 Lithium
Phenothiazine 3 Chlorpromazine, fluphenazine,
etc.
Butyrophenones 3 Haloperidol
Benzodiazepines 4 Alprazolam, lorazepam, etc.
Miscellaneous
Chemotherapeutics 2 Cisplatin, Fludara
Musculoskeletal 2 Botulinum toxin A Should not be used without discussing with
agents neuromuscular specialist
(1) Contraindicated, avoid in MG even if the disease is controlled; (2) likely to

worsen MG, systemic administration only with available ventilation support in a
hospital; (3) may worsen MG, usually well tolerated but use with caution; (4)
have caused in rare cases, usually not a problem for the majority of MG patients
Besides drugs, electrolyte imbalances may be associated with increased

muscle weakness. Hypermagnesemia is the most prominent cause as magnesium
acts as an antagonist to calcium during neuromuscular transmission.
Hypermagnesemia is mostly iatrogenic like preeclampsia/eclampsia therapy.
Serum magnesium levels are not always consistent with clinical course, so
weakness should be carefully assessed.
Moreover iatrogenic MG has been defined with penicillamine, interferon
therapy, and bone marrow transplantation. Symptoms are usually mild among
these subjects, and MG is most often reversible with the discontinuation of the
therapy, i.e., penicillamine and interferon. Onset after bone marrow
transplantation varies between months to years. These patients require
exceptional surgery.
8.4.2 The Myasthenic and the Cholinergic Crises

Crisis is defined as a need for mechanical ventilation due to respiratory muscle
weakness. In patients with MG, there is a risk of developing two kinds of crises
with different therapeutic approaches: the myasthenic and the cholinergic crises.
The myasthenic crisis is rather an exacerbation: It can be caused or provoked by
factors like respiratory infections, emotional stress, and surgery. Specific
immunotherapies (plasma exchange or intravenous immunoglobulin) are
associated with a rapid recovery in few days in most of the cases [6]. A limited
group of myasthenic crisis requires weeks to resolve with vigorous
immunosuppressive therapy with underlying cause if it exists. Residual effects of
long-lasting anesthetic drugs may also impair neuromuscular function in early
postoperative course as in myasthenic crisis.
The cholinergic crisis may also appear with muscle weakness with even need
for invasive mechanical ventilation. However, the main etiological factor is an
overdose with cholinesterase inhibitors, and clinical presentation is with signs or
symptoms associated (e.g., excessive salivation, sweating, abdominal cramps,
urinary urgency, bradycardia, muscle fasciculation or weakness). Differential
diagnosis may be problematic in some cases necessitating a single dose of
edrophonium. This agent would improve symptoms in a myasthenic crisis, but
they will worsen or not be changed in a cholinergic crisis.
8.4.3 Therapy
The treatment consists of medical and surgical modalities. For an appropriate
management of the perioperative period, it is useful to have some information
also about the medical treatment of the patient, for it can be crucial in
determining the optimal timing for the operation. The most important and
common way of treatment is still symptomatic: Improving neuromuscular
transmission is the key approach and achieved with an anti-AChE, mainly
pyridostigmine [7, 11]. The drug results in increased ACh levels at
neuromuscular junction as it decreases ACh degradation. The response to
therapy may not be uniform for muscle groups [7].
Patients with anti-MuSK are less likely to respond pyridostigmine therapy
[12]. In case of severe muscarinergic side effects, glycopyrronium bromide,
atropine sulfate, and loperamide can be used.
Regarding the immunosuppressive therapy, corticosteroid therapy has been
shown to be beneficial on slowing the progression [13]. Other alternatives for
immunosuppressive therapy include azathioprine, cyclophosphamide,
cyclosporine A, tacrolimus, and rituximab [6]. Patients under tacrolimus and
cyclosporine therapy should be investigated preoperatively about renal
impairment.
Plasma exchange and intravenous immunoglobulin are appropriate for
myasthenic crisis or severe myasthenia [14]. However, both modalities can be
performed prior to surgery to optimize neuromuscular function. Timing of
surgery should be planned close to these aforementioned therapies in order to get
the maximum benefit.
Myasthenic crisis is an emergency case and has to be treated under
“intensive care” conditions with respiratory support, treatment of infections, and
monitoring of vital functions and mobilization. Intravenous immunoglobulin
(IVIG) and plasma exchange are options for further treatment; both can be given
in sequence if necessary, as patients can respond to one but not to the other [15].
Treatment of cholinergic crisis includes endotracheal intubation, atropine,
and cessation of cholinesterase inhibitors until the crisis is over.
8.5 Preoperative Evaluation

Elective surgery for myasthenic patients should be reserved for a stable period of
the disease when the medication requirement is minimal for uneventful
perioperative course. It is mandatory – although not sufficient – to obtain
neurological optimization in order to ensure an early and safe recovery in
postoperative period. It should be kept on mind that vigilant preoperative
assessment by an experimented anesthetist is the first step to reduce
complications and need for ICU. Management with an experienced team would
be rational to distinguish high-risk myasthenic patients and to diagnose and to
treat acute postoperative complications. If acute cases with a high possibility of
myasthenic crisis are presented, more aggressive strategies such as
plasmapheresis or intravenous immunoglobulin can be necessary for the
operative preparation [15].
Prediction of postoperative myasthenic crisis (POMC) would be very
beneficial, both because of possible preventive approaches and also to plan a
postoperative ICU admission. A recent article proposes a new predictive score of
POMC (Table 8.3) [16]: Regarding this system, patients with a score of <2.5
have the probability of having a POMC of less than 10 %, while a score of >4.0
is associated with a POMC probability of approximately 50 %.
Table 8.3 A new postoperative myasthenic crisis score [16]
Variables associated with POMC Assigned points (0–8.5)
Osserman scale
Stage I–IIA 0
Stage IIB 1
Stage III–IV 3
Duration of myasthenia gravis (year)
<1 0
1–2 1
>2 2
Lung resection
No 0
Yes 2.5
BMI
<28
≥28 1
POMC postoperative myasthenic crisis, BMI body mass index
Anti-AChE therapy on the morning of surgery is associated with two

different approaches. Suspension of anti-AChE therapy can reduce
neuromuscular block requirements, but it may also decrease neuromuscular
recovery in early postoperative period [17]. Therefore, maintenance of
pyridostigmine is generally accepted as essential for physiologic recovery in
adults [18, 19].
Coexisting diseases should be carefully investigated, especially those which
would affect patient’s recovery such as thyroid disturbances as it affects
neuromuscular recovery [7].
Routine premedication with opioids or common sedatives should be avoided
or performed very carefully because they can depress the respiration. While
sedating these patients, drugs having no effect on respiration (such as
dexmedetomidine) can be preferred.
8.6 Perioperative Anesthetic Management

Thymectomy in indicated patients can be performed either via sternotomy
(“open”) or with minimally invasive methods (video-assisted thoracoscopic
extended thymectomy (VATET) or robotic surgery). The advantages of VATET
compared to open surgery were defined as reduced stress, lowered pain scores,
early mobilization, and diminished length of stay [20–22]. Besides these benefits
thoracoscopic surgery presents, a new challenge for the anesthesiologist is the
inevitable use of neuromuscular blocking agents (NMBAs) for lung isolation as
well as double-lumen tube insertion.
Indeed, in MG, use of NMBAs should be avoided, “if possible.” The use of
succinylcholine is not recommended at all, as response to depolarizing agent is
variable with higher doses than healthy subjects and dual block becomes a
potential risk. Regarding the use of nondepolarizing agents, the effects and
duration of action can vary depending on the preoperative precautions (such as
maintenance or discontinuation of pyridostigmine). Therefore, there are several
series and case reports where alternative methods such as high-dose desflurane
[23] or thoracic epidural anesthesia [24] have been used to avoid the NMBAs in
open thymectomy and in other operations than thymectomy. In a recent cohort
study, the success rate of anesthetic management for MG without NMBA was
found to be 71.1 %. Interestingly, subjects requiring mechanical ventilation came
from NMBA-free groups (5 %) [25]. However in VATET, one-lung ventilation
(OLV) is absolutely indicated; as a consequence, NMBAs are necessary for
several reasons [19]:
Successful positioning of double-lumen tubes can be very difficult in
patients without NMBAs.
A totally “silent” lung is obligatory for a successful operation.
Spontaneous breathing efforts are not desired during OLV as it can confer
with surgical comfort.
For lung isolation, successful applications of bronchial blockers have also
been reported in complicated cases [26].
The differences in sensitivity between the different types of nondepolarizing
NMBAs in MG appear to be very small. Mivacurium, a short-acting NMBA,
differs by elimination mechanism (hydrolysis by plasma cholinesterase).
Pyridostigmine therapy was suspected to increase elimination of mivacurium. It
has been shown that reduced dose of mivacurium is associated with adequate
muscle relaxation and safe extubation [19]. Intermediate-acting NMBAs such as
rocuronium, cisatracurium, and vecuronium have similar effects on MG patients.
Empirically, 50 % of the standard dose is suggested to be adequate, albeit with
an increased risk of prolonged recovery. A recent study has shown that baseline
train-of-four (TOF) ratio and age of disease onset are determinants of the
increased response to rocuronium in MG [27].
Neuromuscular monitoring (i.e., train-of-four or TOF) is crucial both to
achieve adequate relaxation and moreover to ensure safe recovery (TOF > 90) at
the end of surgery. In adult MG, TOF is a part of standard monitoring
independent of NMBA administration [18, 27, 28]. When reversal agents are
available, TOF would be beneficial to assess objectively timing and dosing. TOF
should be an obligatory monitoring in all myasthenic patients (also in other
operations than thymectomy). Only a calibration before the administration of
NMB can make sense; therefore, the monitoring should start before the induction
[29] and continue until a TOF ratio of >0.9 (rather 1.0) has been obtained.
Generally, drugs that can even potentially affect the respiratory effort (e.g.,
benzodiazepines and opiates) should be avoided. Volatile anesthetics are known
to affect neuromuscular transmission in a dose-dependent manner. Inhibition of
postsynaptic nicotinic ACh receptors seems to have significant role with other
possible mechanisms. This effect is more pronounced among myasthenic
patients whose preoperative TOF ratio is less than 90 % [28]. Sevoflurane has
been showed to depress T4/T1 ratio at two MAC both in myasthenic and healthy
subjects [28]. Similarly desflurane has been shown to achieve comfortable
intubation conditions and fast recovery as propofol [17].
Sugammadex (yet not approved by FDA) is a selective NMBA-binding agent
designed to reverse the effect of the steroidal NMBA rocuronium and also
vecuronium [9]. It decreases the amount of free NMBA molecules by binding
the molecules making them ineffective without any intervention with the AChR
or the anticholinesterases. The use of sugammadex in MG patients has been
described in relative larger series in recent publications [30, 31]. Generally, use
of sugammadex after (diminished doses of) rocuronium showed faster reversal
and no postoperative complications. However, it must be noted that there are
some case reports showing that sugammadex was not effective in the reversal of
rocuronium in MG [32, 33]. Obviously, sugammadex is a new drug, and
scientific and practical experience is still necessary in different patient
populations including MG. For now, it is suggested as a very potential beneficial
improvement.
8.6.1 Juvenile MG
Juvenile MG is often anti-AChR type and responds to thymectomy. As in adults,
plasmapheresis or intravenous immunoglobulin G is indicated for refractory MG
or prior to operation [34].
The benefits of thymectomy in JMG have been reported in recent series [35,
36]; furthermore, another study comparing open and thoracoscopic approaches
has reported a significant decrease in hospital stay [38].
The largest series in juvenile MG reported 40 children, about one half (17 of
40) of whom was assessed as severe MG [37]. In this study, TOF monitoring
was a part of monitoring of JMG patients, and with the use of reduced dose of
rocuronium (1× ED95), TOF recovery greater than 1 h was not observed.
Sugammadex was used safely also in this patient group.
An additional challenge for the anesthetic management of JMG is airway
management for the pediatric OLV (this is actually also a general problem, even
without MG). In one series, thoracoscopic thymectomy was managed without
muscle relaxation in 20 children [36], whereby endotracheal intubation was
achieved with single-lumen tube which does not necessitate a deep muscle
relaxation. On the other hand, the benefits and necessities of lung isolation
should also be considered. Double-lumen tubes (left, 28 or 32 Fr) are preferred
among relatively older children (i.e., above 30 kg). For smaller children,
endobronchial blockers with guidance of pediatric fiber-optic bronchoscope (3.7
mm) constitute a reliable alternative; however, its usage necessitates an
experienced thoracic anesthetist familiar with pediatric cases [35].
8.7 Postoperative Follow-Up

Postoperative follow-up for MG begins with total recovery of neuromuscular
function. Besides spontaneous breathing efforts, upper airway reflexes should be
intact, which can be quite objectively decided by a TOF ratio of >90 %.
Monitoring of TOF is also recommended during the immediate postoperative
period. Clinical evaluations (such as a head lift > 5 s in the conscious patient) are
also helpful, but they are inferior to TOF monitoring and tongue-depressor test.
Adequate tidal volume, trigger level, or blood gas analysis can also help to
assess respiratory muscle function.
Residual curarization should be prevented by TOF monitoring and by
reversal drugs if needed. Maintenance of the recent treatment (including anti-
AChE therapy) helps physiologic recovery and should be preferred.
Effective analgesia is essential, not only to preserve pulmonary function but
also to prevent a postoperative myasthenic crisis. For VATET, paravertebral
analgesia with long-acting local anesthetics can be the method of choice. For
open thymectomies and other operations, epidural analgesia/anesthesia is
associated not only with a decrease in perioperative NMBA use but also an
adequate postoperative analgesia. Intercostal blocks can be used solely or –
better – as an adjunct to paravertebral or epidural analgesia. Generally, non-
opioid analgesics should be preferred; NSAID or acetaminophen or
dexmedetomidine can be used, although the interactions of these drugs have also
not been examined in studies. If systemic opioids are inevitably required, small
doses of short-acting opioids should be desirable.
Respiratory failure is a rare but serious complication. Differential diagnosis
consists of residual effects of anesthetics, myasthenic crisis, and cholinergic
crisis. Myasthenic crisis can be related to ongoing infection, hormonal factors,
and surgical stress. The incidence has been reported between 6 and 34 % [16, 39,
40]. In two large newer series, myasthenic crisis was observed in less than 10 %
of the patients [16, 39]. Related factors varied between centers such as history of
myasthenic crisis, uncontrolled myasthenia, higher body mass index,
combination with lung surgery or severe MG, and also impaired lung function or
decremental response of orbicularis oculi muscle [16, 39, 40]. Symptoms present
as a consequence of fatigue of the pharyngeal and respiratory muscles. Patients
with residual anesthetic effects may benefit from noninvasive ventilation. In case
of myasthenic crisis, immunomodulation is preferred with treatment of
underlying cause like infection. Plasmapheresis or intravenous immunoglobulin
should be administered quickly to limit crisis. In such cases, mechanical
ventilation may often be necessary.
Cholinergic crisis is associated with an excess of ACh in both muscarinic
and nicotinic receptors. Overstimulation of nicotinic receptors results
involuntary twitching, fasciculation, and weakness which can be explained with
inability to coordinate contraction and relaxation. Treatment consists on
discontinuation of anti-AChE therapy.
Routine admission to the intensive care unit (ICU) with mechanical
ventilation should be avoided because of several reasons such as increased
infection risk, airway-associated morbidity, and not at least stress-induced
myasthenic crisis.
An uneventful course is possible only with a multidisciplinary approach.
Patient should be prepared for thymectomy with optimal physiological
conditions. This group of patients benefit mostly of minimal invasive
alternatives with reduced surgical stress. Preoperative evaluation is the
cornerstone of anesthetic management, and the anesthesiologist should be
familiar with the clinical course of MG. Weaning from mechanical ventilation
begins at preoperative visit when planning perioperative treatment; fast-track
strategies are suitable for this group.
Conclusion
The increasing number of thymectomy and especially of VATET in MG
necessitates an adequate knowledge of MG. This would help in differential
diagnosis of possible postoperative problems. ICU admission is rarely required;
however, it may be challenging because of possible interactions of different
drugs (i.e., NMBs, anti-AChE, and others), comorbidities, and non-concrete
prediction of the treatment facilities. Therefore, ICU admission should be
avoided as possible. An appropriate pre- and perioperative approach would help
to decrease the postoperative ICU admission and prolonged mechanical
ventilation.
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DOI 10.1007/978-3-319-19908-5_9
9. How About Esophagectomies?

Tamás Végh1, 2
(1) University of Debrecen, Department of Anesthesiology and Intensive Care,
Debrecen, Hungary
(2) Outcomes Research Consortium, Cleveland, OH, USA

Tamás Végh
Email: veghdr@gmail.com
9.1 Indications of Esophagectomy

Surgical procedures of the esophagus are very unique and difficult in terms of
surgery, anesthesia, and postoperative care. The reason is that esophagus passes
through three regions of the body, so surgical procedure may be performed in the
cervical, thoracic, and abdominal region or in more than one region in same
time.
The most common reason for esophagectomy is cancer; however, it can also
be a result of Barrett’s esophagus, hiatus hernia, achalasia, stricture, rupture of
the esophagus, or congenital conditions.
The two most common types of esophageal cancer are squamous cell
carcinoma, originating in the thoracic part of the esophagus, and
adenocarcinoma, which arises from the glandular cells lining in the distal part of
the esophagus and at the esophagogastric junction.
The preferred treatment for esophageal cancer is surgery. However, for many
patients, surgery is combined with chemotherapy, radiation therapy, or hormone
therapy. These nonsurgical treatments may be administered before surgery
(neoadjuvant therapy) or after surgery (adjuvant therapy) [1–5].
9.2 Types of Esophagectomy
Esophagectomy is a high-risk procedure, and the complication rate is high due to
the anatomic challenges of the procedure. Esophagectomy may be done using
either of two main types of techniques: open and minimal invasive method. In
the standard, open technique, the surgeon operates through one or more large
incisions in the neck, chest, or abdomen.
The choice of surgical approach depends upon the tumor location,
submucosal extension, adherence to the surrounding tissues, the conduit to be
used to restore gastrointestinal continuity, and the extent of lymphadenectomy
[6] (Table 9.1). Although the gastric interposition is most commonly used as a
conduit for reconstruction following esophagectomy, the jejunum or the colon
can also be used as the conduit. These conduits are resistant to the effects of
gastric acid, and they have a shape similar to the native esophagus [21–23].
Table 9.1 Types of esophagectomy
Resection name Indication Surgical resection Disadvantages
Cervical Carcinoma of Removal of portions of the pharynx, the larynx,
esophageal the cervical the thyroid gland, and portions of the proximal
resection esophagus esophagus. This one-stage, three-phase operation
requires cervical, abdominal, and thoracic
incisions and a permanent terminal tracheostomy
[7, 8]
Transhiatal Cervical, Upper midline laparotomy incision and a left neck Inability to
esophagectomy thoracic, and incision, typically without a thoracotomy. The perform a full
esophagogastric thoracic esophagus is bluntly dissected through the thoracic
junction cancers diaphragmatic hiatus superiorly and via the neck lymphadenectomy
inferiorly. A cervical anastomosis is created most
often with a gastric pull-up approach [9, 10]
Ivor-Lewis Cancers in the Laparotomy with a right thoracotomy and an Leak occurring at
transthoracic lower third of intrathoracic esophagogastric anastomosis the intrathoracic
esophagectomy the esophagus allowing a full thoracic lymphadenectomy anastomosis is
associated with
high morbidity and
mortality [11–13]
Modified Ivor- Tumors of the Left thoracoabdominal incision with a gastric pull- High incidence of
Lewis gastroesophageal up and an esophagogastric anastomosis in the left complications [14]
transthoracic junction side of the chest
esophagectomy
Tri-incisional Transthoracic total esophagectomy, a
esophagectomy lymphadenectomy, and cervical esophagogastric
anastomosis [15, 16]
Esophagogastric Esophageal An esophagectomy with partial gastrectomy or an
junction cancers at the extended gastrectomy, with or without
resection esophagogastric thoracotomy [17, 18]
junction or intra-
abdominal
esophagus
Minimal Either total endoscopic resection with Prolonged surgical
invasive thoracoscopic or laparoscopic approaches. time, one-lung
approach Advantages are less surgical stress and pain, ventilation in
shorter ICU and hospital stay, decreased incidence prone position that
of postoperative complications combined with may result in
quicker return to working, less intraoperative impaired
blood loss oxygenation [19,
20]
9.3 Preoperative Preparation for Esophagectomy

Preoperative selection and patient preparation are crucial for esophagectomy
because an esophageal resection results in a large physiologic insult to the
patient. Although the mortality from esophagectomy has decreased in the last
decades, adequate patient selection is an important issue of that reduction in
mortality by identifying high-risk patients in whom the procedure would be too
hazardous. During the preoperative evaluation, anesthesiologists have to
consider many factors, including age, cardiac and pulmonary function,
nutritional status, medications, neoadjuvant therapy, and blood transfusion.
Cardiopulmonary function evaluation is the same as for lung resection
procedures [24–26].
9.4 Anesthesia for Esophagectomy

Detailed review of anesthesia for esophagectomy has been previously addressed.
However, there are factors during the anesthesia which have influence on
postoperative period after esophagectomy.
Although the incidence of anastomotic complications decreased in the last
decades, anastomotic complications and perfusion of the conduit are important
issues after esophagectomy, as it has been accounted for 37 % of all hospital
death after esophagectomy. Thoracic anastomoses have lower leak rate than
cervical anastomoses but have higher morbidity and mortality. One of the factors
that are playing role in the incidence of anastomotic leaks is conduit ischemia.
Appropriate tissue oxygenation depends on several variables: vascular anatomy
and tone and blood oxygen tension. How can anesthesiologist improve blood
supply of the conduit? Thoracic epidural anesthesia and the use of
prostaglandins have influence on gastric vasomotor tone; the use of intravenous
nitroglycerin and venous bloodletting can reduce venous congestion. Systemic
hypotension may impair gastric tube perfusion and must be treated. The use of
vasoconstrictors in normovolemic condition has no detrimental effect on gastric
blood flow, and the use of short-acting vasopressors as phenylephrine or
ephedrine is safe and not associated with postoperative anastomotic leak. Before
the use of vasopressors hypovolemia should always be excluded.
Another important anesthesia technique which has influence on
postoperative outcome and complication is ventilation during esophagectomy.
Esophagectomy often requires one-lung ventilation. It has been demonstrated
that lung-protective ventilation with small tidal volume and with the use of
moderate PEEP provides sufficient oxygenation during OLV and resulted in
reduced inflammatory response after esophagectomy, improved lung function,
and earlier extubation [27–29].
9.5 Postoperative Care After Esophagectomy

9.5.1 Timing of Extubation and Supplemental Oxygen
Therapy
Timing of extubation is a crucial issue after esophagectomy. Basically there are
two concepts of extubation after esophagectomy: prolonged ventilation and early
extubation. Before the introduction of thoracic epidural analgesia, studies
suggested prolonged postoperative ventilation up to 2 days. However, prolonged
ventilation has not been shown to decrease incidence of postoperative pulmonary
complications. Moreover, there are disadvantages of this approach: sedation-
related side effects, risk of aspiration, and weaning problems.
The use of thoracic epidural and shorter operative time, early extubation has
been advocated to reduce mortality, morbidity, and cost after esophagectomy.
Early extubation may reduce intensive stay and cost, decreases postoperative
respiratory complications, and does not increase the risk of reintubation.
However, there are conditions that could require prolonged ventilation:
bleeding, hemodynamic instability, respiratory insufficiency, and neurologic
impairment.
After extubation supplemental oxygen administration should be used either
by face mask or nasal cannula (1–6 l/min) for maintaining of oxygen saturation
above 90 %. Supplemental oxygen has advantages after esophagectomy:
decreased incidence of postoperative nausea and vomiting, improved wound
healing, maintenance of adequate cardiac and central nervous function, and
decreased incidence of arrhythmias. There are data that low oxygen delivery
after esophagectomy is associated with the risk of complications [30–32].
9.5.2 Analgesia
Effective analgesia after esophagectomy is a challenging issue in anesthesia. As
we noted above, this procedure often requires an abdominal, cervical incision
and either thoracotomy as well.
Analgesia for thoracic procedures has been discussed extensively in another
chapter of this book. However, it is important to remember that sympathetic
activation caused by surgical procedure and pain manifests as tachycardia,
hypertension, and increased contractility, all of which result in increased
myocardial oxygen consumption. As it has been noted, most of the patients
undergoing esophagectomy have cardiovascular coexisting diseases, especially
ischemic heart disease (IHD). These patients’ response to surgical stress differs
from that of healthy patients. Sympathetic stimulation caused by pain may
constrict post-stenotic coronary arteries and reduce blood supply to the
subendocardium. The difference in oxygen delivery and demand presents as
postoperative myocardial ischemia. The selective sympathectomy using thoracic
anesthesia in patients with IHD can dilate constricted coronary vessels, reduce
heart rate, and improve cardiac function by reducing preload and afterload and
optimizing myocardial oxygen delivery.
The sympathectomy of thoracic epidural analgesia causes vasodilatation in
mesenteric vessels and has been shown to improve bowel function by reducing
the duration of postoperative ileus, enhancing bowel blood. The increase in
bowel motility from unopposed parasympathetic activity is not associated with
any significant increase in anastomotic dehiscence.
In patients in whom thoracic epidural analgesia is contraindicated, there are
several alternative methods. Using intercostal nerve block a catheter is placed in
a paravertebral space just below the level of incision. Effectiveness of this
method is mostly similar to epidural analgesia. Intravenous opioids and
nonsteroid analgesics can work synergistically and can reduce postoperative pain
[33–37].
9.5.3 Fluid Management

Fluid management is also crucial for all thoracic surgeries including
esophagectomy and has been discussed extensively in a separate chapter of this
book. Anesthesiologists should consider a restrictive fluid administration in the
first 24 h (<20 ml/kg, less than 2 L crystalloid and less than 1 L albumin
intraoperatively with less than 3 L of total amount of crystalloids in the first 24
h).
Therefore, close monitoring of intravascular volume status is required, along
with invasive hemodynamic monitoring (arterial blood pressure, central venous
pressure, thermodilution techniques) and urine output [38–41].
9.5.4 Nutrition Considerations

Patients undergoing esophagectomy are frequently malnourished due to several
reasons: stenosis of the esophagus by the tumor, systemic effects of the tumor,
side effects of the chemotherapy, and surgery.
Most common problem in patients with esophageal cancer is difficult
swallowing. These patients eat only soft, easy-to-swallow foods, primarily
consume liquids. Therefore, patients with dysphagia are at risk for deficiencies
in protein, fat, carbohydrate, vitamins, minerals, and total calorie.
Nutritional assessment helps to identify the nutritional status and risk of
malnutrition. Nutritional history and anthropometric parameters can be
inaccurate; however, assessment of the metabolically active body cells by
bioelectrical impedance may solve as a better marker. Assessment of sarcopenia,
defined as loss of skeletal mass and strength, helps to identify high-risk patients
who require perioperative nutrition.
Biomarkers, such as albumin, transferrin, C-reactive protein, prealbumin,
and retinol-binding protein, are also used in assessing nutritional condition
(Table 9.2). However, in postoperative period, accuracy of these biomarkers is
questionable. Medication, inflammation, changes in fluid shift and vascular
permeability, and hepatic and renal function have influence on levels of
biomarkers. However, data are showing that patients with hypoalbuminemia are
at risk of postoperative complications compared with those who have normal
albumin level.
Table 9.2 Biomarkers of nutritional status [44]
Biomarker Normal range Half-life
Albumin 35–50 g/L 12–20 days
Transferrin 2–3.6 g/L 8–9 days
C-reactive protein <10 mg/L 2 days
Prealbumin 160–400 mg/L 12 h
Retinol-binding protein 30–80 mg/L 12 h
There are several nutritional scoring systems for nutritional assessment. The
Subjective Global Assessment (based on patient’s history, loss of subcutaneous
fat, muscle wasting, and presence of edema or ascites) has high sensitivity and
specificity. The prognostic nutritional index is focusing on serum albumin level
and current and usual weight. The Nutritional Risk Screening Score is based on
the severity of nutritional status. An accurate estimation of energy expenditure is
important in patients with nutritional disorders. The traditionally used Harris-
Benedict equation is inaccurate, and the indirect calorimetry is the gold standard
method to measure caloric requirements.
It is known that malnutrition is associated with increased rate of
postoperative complications (including impaired wound healing, loss of muscle
tissue, reduced immunocompetence, depression, apathy, immobility, and
increased frequency of decubitus and ulcer) and delayed recovery.
Benefits have been found when severely malnourished patients received
nutrition support prior to surgery. There are different ways for preoperative
nutrition support. Most physiological route is the enteral way. Dysphagic
patients should be modifying the consistency of food. It can include normal food
with accurate chewing and or soft, pureed and blenderized foods. Patients should
learn to eat frequently and smaller portions, because pureed foods have larger
volume than normal foods containing same calories.
If these modifications are insufficient, there are options for insertion of a
nasogastric or nasojejunal tube, feeding jejunostomy, or percutaneous
endoscopic gastrostomy (PEG). Nevertheless, most of the surgeons do not prefer
the use of PEG because stomach is most frequently used as conduit that forms
the new esophagus.
There are different methods for delivery. Continuous feeding is used if a
patient is unable to tolerate large volumes of feed and usually refers to feeding
over 16–20 h. In this case, feed is delivered by pump. Continuous feeding
usually includes a break of at least 4 h in 24 h to allow the stomach to re-acidify.
The second method is the intermittent feeding that involves periods of feeding
using the pump with breaks. The third way is the bolus feeding involves the
delivery of 100 mls to 300 mls over a period of 10–30 min and can be given four
to six times a day depending on patients’ individual feeding regime.
There are several type of feeds is available. Standard whole-protein feeds
provide 1 kcal/ml, while high-energy feeds provide 1.5 kcal/ml. High-energy
feeds are useful when fluid is restricted or to reduce feeding time. Most feeds are
lactose-, gluten-, and wheat-free and suitable for vegetarians.
There is no need to change the regime in diabetic patients, but blood glucose
level should be monitored frequently.
Feeding tubes should be flushed with water before and after administration
of feed and medication and in between medications.
It is known that enteral nutrition is cheaper than parenteral nutrition, and it is
comfortable, because patients can be fed at home. Nevertheless, in severely
undernourished patients who cannot be fed adequately orally or enterally,
preoperative parenteral nutrition is indicated. Moreover, parenteral nutrition
requires hospitalization and sophisticated nursing.
Surgical stress leads to insulin resistance and increases blood glucose levels.
In diabetic patients, blood glucose should be monitored every 4–6 h. Guidelines
suggest that blood glucose be maintained between 5.5 and 11 mmol/l in stressed
patients and then tightened to 5.5–8.5 mmol/l once control is established.
Good oral hygiene is essential for patients receiving nutritional support or nil
by mouth. Saliva is normally produced when eating and keeps the mouth clean.
However, saliva production is often reduced during nutritional support and the
oral mucosa can develop sores. Patients should be encouraged to brush their
teeth regularly and use a suitable mouth rinse [42–52].
9.5.5 Blood Administration

Regardless of the specific approach (transthoracic versus transhiatal),
esophagectomy with lymphadenectomy represents a major operation with a
mean operative blood loss of 3–500 ml approximately. The use of neoadjuvant
chemotherapy can cause bone marrow suppression and anemia in patients
undergoing esophagectomy. All of these factors require consideration of
administration of blood transfusion in the perioperative period. Nevertheless,
there are evidences that blood transfusion may worsen the oncologic outcome,
though these reports were uncontrolled. Patients who received blood transfusion
have had larger tumors, more sever medical conditions. Therefore, the
relationship between cancer recurrence and death has not been clearly proven.
The ideal perioperative hemoglobin level is not clear. Keeping the
hemoglobin level above 100 g/l is poorly supported with evidences. Recently, in
hemodynamically stable patients, the transfusion trigger is 70 g/l.
There are evidences that the use of allogenic blood transfusion decreases
survival and increases the incidence of cancer recurrence, compared with the use
of autologous transfusion [53, 54].
9.5.6 Deep Vein Thrombosis Prophylaxis

Postoperatively, a majority of thoracic surgery patients are not able to move
because of pain, respiratory distress, and age. The lack of ambulation can result
in a blood stasis in lower extremities; this increases the contact time between
blood and vein wall irregularities, helping a blood clot formation. The incidence
of deep venous thrombosis in patients in medical and surgical intensive care
units is about 10 % to 30 %. Prophylaxis with mechanical (compression
stockings are applied to both lower extremities) and pharmacological methods
(heparin shots are given subcutaneously twice a day) has been shown to be
effective and safe in most types of surgery and should be routinely implemented.
Both subcutaneous, low-dose unfractionated heparin (LDUH) and low-
molecular-weight heparin (LMWH) have been shown to reduce the risk of
venous thrombosis. Low-dose unfractionated heparin use does not interfere with
epidural catheter placement or removal. However, LMWH should be held for
12–24 h before epidural placement or removal, to decrease the risk of hematoma
formation. The use of LMWH for 2–3 weeks after hospital discharge in patients
undergoing major cancer surgery may reduce the incidence of asymptomatic
deep venous thrombosis.
Until patients are ambulating independently, they should keep the stockings
on when in bed. Encourage early ambulation as well as leg and ankle exercises.
Early mobilization of patients includes getting them out of bed to a chair the first
postoperative day and three times each day thereafter [54, 55].
9.5.7 Management of Drainage Tubes

Chest tubes are indwelling catheters placed into the pleural space to evacuate air
and fluids and maintain a physiological negative pleural pressure. Air collects at
the less dependent part (apically or retrosternal, depending on patient’s position),
and fluid collects at the lower part of the chest cavity. That’s why most guideline
recommends the use of two chest tubes.
In the absence of air leak (50 ml/min in 12 h or less than 20 ml/min in 8 h),
most postoperative chest tube removal protocol is based on quantity and quality
of secretions. If bleeding, chylothorax, or empyema does not exist, the normal
daily pleural secretion is about 350 ml. Most surgeons remove chest drains if the
daily secretion is less than 300 ml.
If an air leak exists, a digital drainage system with continuous suction with
(minus15 cmH2O) is recommended. If air leak reach less than 50 ml/min in 12
or 20 ml/min in 8 h, chest tubes are removable.
As chest tubes are playing major role in postoperative pain, their early
removal appears to accelerate postoperative recovery [56, 57].
9.5.8 Physiotherapy
Respiratory complications are frequent after esophagectomy. The benefits of
physiotherapy in the perioperative period have been shown by numerous studies.
It has been showed that preoperative physiotherapy (e.g., inspiratory muscle
training) for two or more weeks before cardiac surgery reduced the incidence of
pulmonary complications. Preoperative physiotherapy is also feasible for
patients undergoing esophagectomy to preserve respiratory muscle strength.
There are two main types of breathing exercises: active cycles of breathing
and using incentive spirometry. Both techniques aim to re-expand the lung with
maximum sustained and fractional inspiration and clear airways with assisted
cough.
For both types of exercises, patients must be in upright position either in bed
or chair. During active cycle of breathing, patients must place hand over upper
abdomen and take slow deep breaths and hold for 3–5 s and repeat four to five
times. After this cycle, the patient has to huff as this maneuver helps move
phlegm to clear.
Using incentive spirometer, patient inhales from the spirometer and holds
breath as long as it is possible. This should be practiced up to ten breaths per
hour. It is important to mobilize patients as soon as possible after esophagectomy
to prevent postoperative complications such as pneumonia and deep vein
thrombosis. At the first day, the aim is to sit in chair that can help to improve
lungs by increasing the depth of each breath. By the second postoperative day,
patients should aim to walk with assistance on the ward and increase gradually
the exercise tolerance.
Due to the wound and chest drains, patients may be reluctant to move arm on
the operated side. It is important to practice shoulder mobility to prevent joint
stiffness [24, 58–61].
9.6 Management of Complications After Esophagectomy

Complications after esophagectomy include pulmonary complications (including
pleural effusions, atelectasis, chylothorax, pneumonia, respiratory failure, and
pulmonary embolism) as well as wound infection, empyema, bronchopleural
fistula, recurrent laryngeal nerve injury, cardiac complications such as
arrhythmias and atrial fibrillation, and complications of the conduit.
9.6.1 Anastomotic Leak

Esophageal anastomotic leak is a serious complication after esophageal surgery.
Incidence is about 14 %, and the associated mortality is between 5 % and 35 %.
Anastomotic leak or perforation occurs because of several conditions (ischemia
or distention of conduit, poor nutrition, low serum albumin level, pressure at
suture lines and anastomotic tension, intraoperative bleeding, tumor at resection
margin, use of colon as conduit, drain contacts with the anastomosis). Leakage
of digestive fluids, saliva, overgrowth of bacteria, and fungi in the
perianastomotic tissues can lead to severe inflammation.
Clinical presentation of the anastomosis insufficiency depends on the size
and location of the dehiscence. Symptoms of the thoracic leak could be fever,
leukocytosis, chest pain, arrhythmia and hypotension, fulminant sepsis, and
increased output through the drains, while cervical leak can be present as a
simple neck infection.
Integrity of the anastomosis can be evaluated with swallowing methylene
blue or using water-soluble contrast agent.
Although most of the anastomotic leakage can be managed conservatively
with drainage and broad-spectrum antibiotics, in severe cases surgical approach
may be required.
Treatment is determined by the location and size of the leak. If the leak is at
the cervical anastomosis, the neck wound is opened to allow drainage and
healing over time. This can lead to stricture which requires dilation, but that is
usually not incapacitating. The patient should generally be kept nothing per os to
reduce the pressure and fluid draining past the hole. Administration of antibiotics
that provide coverage for aerobes and anaerobes (ampicillin/sulbactam 3 g every
6 h or piperacillin/tazobactam 3.375 g every 6 h or a carbapenem) must be
initiated along with adequate drainage. In case of beta lactam hypersensitivity,
administration of clindamycin (900 mg every 8 h) with ciprofloxacin (400 mg
every 12 h) is appropriate. Antifungal coverage (400 mg fluconazole in a single
dose) is recommended in selected cases. Swallow test with methylene blue is
repeated 1 week after the initial test. If the leak is smaller, the nasogastric tube
can be removed and the patient can drink clear fluid. As the leak healed, the
patient’s diet is advanced to a normal diet. If the leak is more than a quarter of
the circumference of the anastomosis, surgical intervention should be
considered.
In case of intrathoracic anastomotic leakage, contamination of pleural cavity
or mediastinum may occur. A leak into the pleural cavity should be drained with
chest tubes. Fasting by mouth is necessary. Intravenous antibiotics should be
administered unless the patient has no signs of infection (fever, leukocytosis,
decrease of procalcitonin, and CRP level). Leakage of mediastinal anastomosis
and resulted mediastinitis may remain undetected for prolonged time and can be
fatal if it is not evacuated [62–65].
9.6.2 Anastomotic Stricture
Stricture after esophageal resection can occur at different places: at the
anastomosis, at the diaphragmatic hiatus, or at the pylorus. Stricture may be
secondary to technical problems, ischemia, leak, ulceration, or reflux, and it may
be multifactorial. Most strictures can be treated with either balloon or bougie
dilation [66, 67].
9.6.3 Conduit Ischemia

The viability and function of the esophageal conduit are the most important
factors affecting postoperative outcome and quality of life. It can be difficult to
diagnose the conduit ischemia in the postoperative period after esophagectomy.
Average rates of ischemic complications for stomach, colon, and jejunum are 3.2
%, 5.1 %, and 4.2 %, respectively. Signs of infection, elevated level
inflammatory markers (C-reactive protein, procalcitonin), and symptoms
(tachycardia, respiratory failure, fever, leukocytosis, or any evidence for graft or
anastomotic leak) should suggest problems due to insufficient blood supply of
the conduit. The diagnostic tools include contrast esophagography, endoscopy, or
direct operative inspection. Without treatment conduit ischemia can lead to
further morbidity or mortality. Treatment for mild cases may be supportive, with
or without management of anastomotic leak. In more severe cases of necrosis
debridement, takedown of the anastomosis and creation of an esophagostomy are
recommended [68, 69].
9.6.4 Functional Conduit Disorders

9.6.4.1 Postgastrectomy Syndrome
Postgastrectomy syndromes include small capacity, early and late dumping
syndrome, postvagotomy diarrhea, afferent loop syndrome, efferent loop
syndrome, alkaline reflux gastritis, roux stasis syndrome, anemia, and metabolic
bone disease (impaired absorption of calcium, vitamin D, vitamin B, iron,
copper).
Dumping syndrome may occur due to the loss of pyloric regulation and
receptive relaxation. This can lead to rapid emptying of stomach contents into
proximal bowel. Early dumping is initiated 10–30 min after ingestion.
Symptoms are nausea, vomiting, feeling of postprandial epigastric, fullness,
crampy pain, and belching, explosive diarrhea. Dumping syndrome can be
accompanied or followed by cardiovascular symptoms (tachycardia, palpitations,
diaphoresis, light-headedness).
Pathophysiologic mechanism of early dumping syndrome is that rapid entry
of hyperosmolar chyme into the small bowel triggers rapid fluid shifts from the
intravascular space to the gut lumen to maintain isotonicity and this leads to gut
distention. This fluid shifts can cause hypotension, triggering autonomic
catecholamine surge. Early dumping syndrome can be diagnosed with oral
administration of 50 g glucose as a provocative test. Therapy of early dumping
syndrome is based on control of feeding that includes frequent small meals,
separation of solid foods and liquids, and avoiding high-carb meals.
Late dumping syndrome usually occurs 2–3 h after meals and much less
common than early dumping syndrome. Pathophysiology of this syndrome is
different from the pathophysiology of the early dumping syndrome. In this case
rapid delivery of sugars into small bowel causes hyperglycemia and increase in
insulin release, inducing a marked hypoglycemia. Concomitant insulin shock
causes catecholamine release with tachycardia, tachypnea, diaphoresis,
palpitation sensations, and confusion. Medical management is dietary
modification or surgery in refractory cases.
The postvagotomy diarrhea for the vast majority is not severe and resolves
after several months. In severe form, it may be 10–20 episodes per day which are
often explosive, and often there is no temporal relationship with food. It may
occur at all times (during sleep) and may result in weight loss, malnutrition, and
weakness. Explanation of the syndrome is that vagal denervation leads to
intestinal dysmotility and rapid gastric emptying of liquids. Postvagotomy
diarrhea is much less common after highly selective vagotomy. Complications
could be hypoacidity, malabsorption of bile acids, and bacterial overgrowth in
the proximal bowel. Therapy contains more fiber intake, frequent small meals,
decreased carbohydrate intake, oral administration of neomycin to treat bacterial
overgrowth, and administration of antidiarrheal agents such as loperamide.
Afferent and efferent limb syndrome may be acute, completely obstructed or
chronic, and partially obstructed. The syndrome can manifest at any time from
the first postoperative day to many years after surgery. The acute form usually
occurs in the early postoperative period (first to second week), but it has been
described to occur 30–40 years after surgery [70–72].
9.6.4.2 Reflux
Gastroesophageal reflux is a common phenomenon in patients after
esophagectomy. Loss of the lower esophageal sphincter plays a key role in the
emergence of reflux. The lower portion of the stomach remains in the abdomen
under positive intraperitoneal pressure, while the upper portion of the stomach is
in the thoracic cavity under negative intrathoracic pressure. Patients after
esophagectomy need to be counseled to eat and drink in the upright position and
remain upright for at least 2 h after eating. The head of the bed should be
elevated 30°, or they should sleep on a foam wedge to avoid regurgitation and
aspiration. Avoiding damage to the recurrent laryngeal nerves helps to prevent
from aspiration when reflux occurs [73, 74].
9.7 Summary
Due to the prolonged and complex surgical procedure and poor preoperative
condition of the patients, esophagectomy leads to significant mortality and
morbidity. Surgical technique, adequate analgesia, careful anesthesia, strictly
controlled fluid management, and optimal timing of extubation may decrease the
incidence of complications (respiratory, cardiac complications, and problems of
the conduit). Inadequate preoperative diet also contributes in increased mortality
and morbidity. Adequate nutrition is a crucial issue after esophagectomy.
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DOI 10.1007/978-3-319-19908-5_10
10. Do the New Hemodynamic Monitoring

Devices Make Sense Compared to the
“Classical” Ones?
Giorgio Della Roca1
(1) Medical University of Udine, Department of Anesthesia and Intensive Care
Medicine of the University of Udine, Udine, Italy

Giorgio Della Roca
Email: giorgio.dellarocca@uniud.it
10.1 Introduction
Postoperative hemodynamic monitoring of high-risk patients, including those
who undergone thoracic surgery, should be inside the modern concept that
insufficient tissue perfusion and cellular oxygenation due to hypovolemia and/or
heart dysfunction is one of the leading causes of perioperative complications in
terms of morbidity and mortality. The modern and new various available
hemodynamic monitoring systems should be used to guide cardiovascular and
fluid management in the perioperative period in high-risk surgical patients [1–5].
The risk of perioperative complications is related to patient status and
comorbidities (Table 10.1), the type of surgery performed and its duration, the
degree of urgency, the skills and experience of the operating and anesthetic
teams, and the postoperative management. Insufficient tissue perfusion and
cellular oxygenation due to hypovolemia and/or heart dysfunction is one of the
leading causes of perioperative complications and poor outcomes [6–9].
Effective fluid management to prevent and treat hypo-/hypervolemia and
titration of vasoactive drugs for heart dysfunction is thus crucial to maintain
adequate oxygen delivery (DO2) and prevent fluid overload and its consequences
[10–12]. Selecting the most appropriate hemodynamic monitoring device (for
diagnosis and to guide therapies) may, therefore, be an important first step in
reducing the risk of complications.
Table 10.1 High-risk surgical patient definition
10.2 Basic Hemodynamic Monitoring

Blood pressure is a variable influenced by both cardiac output (CO) and vascular
tone; hence, blood pressure can remain within the normal range in the presence
of low-flow states, including hypovolemia, as a result of increased peripheral
vascular resistance. Similarly, heart rate may fail to reflect the development of
hypovolemia under anesthesia [13].
Combining and integrating parameters from various hemodynamic
monitoring systems may help improve our understanding of hemodynamic status
[14].
Continuous arterial pressure invasive measurement helps identify the rapid
fluctuations in arterial pressure that may occur in high-risk patients. Artifacts
(over- or under-damping) should be carefully identified and eliminated,
especially when systolic-diastolic components and waveform have to be
analyzed. Noninvasive techniques for continuous measurement of blood pressure
are usually performed in peripheral arteries and may become unreliable in case
of vasoconstriction or low peripheral flow.
Changes in central venous pressure (CVP) with concomitant CO variations
can give an indication of RV function and potential peripheral venous
congestion, an important factor for organ perfusion [15]. In addition, careful
checking of the CVP wave may help to diagnose tricuspid regurgitation with a
“v” wave during systole. When the CVP is low with a concomitant low CO,
there is some degree of hypovolemia, although changes in CVP correlate poorly
with changes in CO [16].
10.3 Cardiac Output Monitoring

The perioperative period is characterized by large variations in whole body
oxygen consumption (VO2). The main goal in this period is to maintain an
adequate DO2 to meet the fluctuating tissue oxygen requirements. Global DO2 is
determined by CO and the oxygen content of arterial blood (CaO2) so, after
correction of hypoxemia and anemia (topics that will not be treated here),
maintenance of an adequate CO is the next logical step to improve DO2. There
are various methods available for monitoring CO: calibrated and not calibrated
[17–21].
10.3.1 Pulmonary Artery Catheter: The “Classical” One

Although criticized during the recent years for its intrinsic invasiveness and no
clear evidence of improved outcomes [22–25], the pulmonary artery catheter
(PAC) is the only tool that provides continuous monitoring of pulmonary artery
(PA) pressure, right-sided and left-sided filling pressures, and CO and mixed
venous oxygen saturation (SvO2). While the PAC can now be replaced by less
invasive hemodynamic monitoring techniques in some cases, in some complex
clinical situations, for example, cardiac surgery, organ transplant surgery, and
surgery associated with major fluid shifts, high risk of respiratory failure, or in
patients with compromised right ventricle (RV) function, the PAC still represents
a valuable tool when used by physicians adequately trained to correctly interpret
and apply the data provided [26, 27]. In such patients, the PAC can be inserted
for limited periods of time and removed when no longer necessary.
10.3.2 Other Cardiac Output Monitoring Devices: The

“New” Ones
10.3.2.1 Pulse Contour Analysis
Stroke volume (SV) can be estimated continuously by analysis of the arterial
pressure waveform, usually derived from an indwelling arterial catheter or by a
noninvasive finger pressure cuff. To calculate SV from a pressure trace, the
algorithms used by these devices have to compensate for the overall impedance
of the system, based on the estimation of compliance and resistance of the
cardiovascular tree. In this regard, optimization of the input signal is imperative,
and severe distortions of the arterial waveform (e.g., severe arrhythmias,
multiple ectopic beats) and inadequate response of fluid-filled transducer
systems (i.e., over- and under-damping) [28] can result in unreliable CO
measurement.
Calibrated Devices
The PiCCOplusTM/PiCCO2 TM system (Pulsion Medical Systems, Munich,
Germany) consists of a thermistor-tipped catheter which is usually placed in
the femoral artery, although catheters for radial, axillary, or brachial
applications are also available. The PiCCOTM device measures CO by
transpulmonary thermodilution, which additionally provides the
computation of volumetric preload parameters (global end-diastolic volume
[GEDV], intrathoracic blood volume [ITBV]), and extravascular lung water
(EVLW). The CO measured by the Stewart-Hamilton principle from the
thermodilution curve is used to calibrate a pulse contour algorithm, which
measures the area under the systolic pulse pressure curve and calculates the
SV in order to provide beat-by-beat CO measurement. The system has to be
frequently recalibrated, at least every eight hours in hemodynamically
stable patients and more often if changes in vasoactive support are provided
[29]. The system has been validated in a variety of clinical settings [30].
The EV1000TM/VolumeViewTM system (Edwards Lifesciences, Irvine,
California) has been more recently introduced, but is analogous to the
PiCCOTM monitor, using pulse wave analysis to calculate CO. A
proprietary thermistor-tipped femoral artery catheter and a separate sensor
are the main components of the system. This system requires calibration by
transpulmonary thermodilution. It has been validated off-line against the
PiCCOTM and transpulmonary thermodilution in critically ill patients [31].
The LiDCOTMplus system (LiDCO Ltd, Cambridge, UK) uses pulse power
analysis to calculate SV and is therefore not technically a pulse contour
device. The algorithm is based on the principle of conservation of mass
(power), assuming a linear relationship between the net power change and
the net flow in the vascular system. This system requires correction for
vascular compliance, with calibration using a transpulmonary lithium
indicator dilution technique performed via an indwelling arterial catheter. It
has been validated in critically ill patients [32, 33].
Uncalibrated Devices (with No External Calibration)
The PulsioFlexTM system (Pulsion Medical Systems) displays trends of
estimated CO by using the patient’s anthropometric and demographic
characteristics (necessary for internal calibration), analysis of the arterial
pressure tracing, and a proprietary algorithm for data analysis. The system
requires a dedicated additional sensor, which can be connected to a regular
arterial pressure catheter. Based on the same pulse contour algorithm used
by the PiCCOTM, the device can be calibrated by entering a CO obtained
from an external source (e.g., Doppler echocardiography) or by the
system’s own internal algorithm.
The LiDCOTM rapid (LiDCO Ltd) device uses the same algorithm as the
LiDCOTMplus system, but instead of lithium dilution, nomograms based on
the patient’s age, weight, and height are used to estimate SV and CO (the
so-called “nominal” SV and CO). An externally estimated CO can be used
to calibrate the device.
The FloTracTM/VigileoTM system (Edwards Lifesciences) consists of a
proprietary transducer (FloTracTM) connected to a standard (radial or
femoral) arterial catheter. Individual demographic variables (age, sex,
height, and weight) and a database containing CO variables derived using
the PAC are used to calculate impedance and a “normal” SV against which
the standard deviation of the pulse pressure sampled during a 20-s interval
is correlated to estimate CO. Arterial waveform analysis is used to calculate
vascular resistance and compliance. The algorithm used by the VigileoTM
device has been modified over time, and recent studies evaluating the
device in the perioperative setting have shown an improved performance
and a significant reduction in the time needed to adapt to vascular
dynamics. In the ICU setting, concerns remain regarding the accuracy in
situations of acute hemodynamic instability as well as hyperdynamic
conditions, although recent software modifications seem to improve the
reliability of CO measurements. The FloTracTM/VigileoTM system has been
shown to be suitable for integration into perioperative optimization
protocols, resulting in improved clinical outcomes [34, 35].
10.3.2.2 Pitfalls in the Interpretation of Cardiac Output

Although CO can be measured with reasonable accuracy and precision with
some of these systems, it is difficult to assess the optimal CO for an individual
patient. A “normal” or even high CO does not preclude the presence of
inadequate regional and microcirculatory flow, and a low CO may be adequate in
a context of low metabolic demand, especially during surgery under general
anesthesia. Moreover, simple identification of a low CO does not tell us what to
do about it. Data acquired can be correctly interpreted by any of the described
devices, but we need to combine/integrate several variables to help decide
whether the CO/SV is adequate and how it can be optimized in the most
effective manner [36–39].
10.3.2.3 How to Select the Best System?

All monitoring systems have unique characteristics in terms of accuracy,
precision, validity, stability, and reliability [18]. Not all monitoring devices have
been evaluated against the same set of criteria, and uncertainty remains
regarding acceptance thresholds for the performance of CO monitors and the
used reference techniques [54–57]. Clinicians must consider the technical
limitations of each monitoring system and the potential trade-off between more
invasive but highly accurate measurements of CO and less invasive but also less
accurate modalities.
Many questions can be raised when considering the choice of CO monitoring
in the perioperative period [40]:
1. Are we ready to accept a less accurate measurement in order to limit

invasiveness? (Fig. 10.1). A less accurate measurement may be acceptable if
the trend analysis is reliable. Cost may also be an important issue.
Fig. 10.1 Perioperative HD monitoring
2. Do we need continuous, semicontinuous, or intermittent measurements?

Most complications after surgery do not have a sudden onset (except sudden
cardiac failure due, e.g., to myocardial infarction or pulmonary embolism)
or an obvious cause (e.g., massive bleeding during surgery), but develop
slowly; therefore, semicontinuous or intermittent measurements may be
acceptable. However, it should be noted that only beat-by-beat measurement
of SV allows assessment of the response to preload-modifying maneuvers,
such as a fluid challenge or passive leg raising (PLR) test.
3. Are calibrated or uncalibrated systems preferable? Non-calibrated systems

are acceptable for the operating room (OR) or the post-anesthesia care unit
(PACU) but may not be suitable for more complex cases, especially in the
ICU. In unstable patients, there is a necessity to “recalibrate” more often
because of frequent changes in vascular tone and also because derived
variables (e.g., EVLW, GEDV) need to be recalculated. A practical option
may be to use an uncalibrated system in the OR/PACU and replace it with a
calibrated system in the ICU.
4. What alarms do we need? A major problem for patient surveillance by

telemetric monitoring is artifact robustness. Any system with too many false
alarms is prone to failure as personnel become desensitized.
5. What kind of monitoring for what kind of patient? This decision is not a
“one size fits all”; rather, the optimal monitoring technique for each patient
will vary depending on the degree of risk and the extent of the surgical
procedure (Fig. 10.1).
10.4 Echocardiography
Although difficult to use as a continuous monitor of CO with conventional
probes, transthoracic (TTE) or transesophageal (TEE) echocardiography can
provide immediate point-of-care assessment of acute hemodynamic changes in
selected patients. Echo techniques can also help to visualize the lungs, but this is
beyond the scope of this review. Obviously, it is not possible to use TEE in all
types of surgery. In addition to the estimation of CO (usually easier with TEE
than with TTE), Doppler echocardiographic examination can provide an
indication of cardiac function, because it allows visualization of the cardiac
chambers, valves, and pericardium [20]. It also allows measurement of the
ejected stroke volume (SV) and derived left ventricular (LV) function
parameters.
TEE provides several views, including:
The LV short-axis view, which can be used to evaluate LV function.
Calculation of the LV fractional area contraction, or the simpler “eyeballing
method,” informs about the kinetic (contractile) state and the shape
(volume) of the heart. Poor contractility may indicate that inotropic support
could help, and “kissing” of the papillary muscle may indicate the need for
fluids if the right heart is functioning normally. The short-axis view may
also be used to identify septal dyskinesia. The finding of a right ventricle D-
shape may suggest the presence of RV dysfunction/failure, indicating a non-
adaptation to an acute increase in RV afterload (pulmonary embolism) or
RV myocardial ischemia.
The four-chamber view, which can help in assessing LV and RV function by
evaluation of the right-to-left size ratio (normal < 0.6).
In more advanced echocardiographic evaluation, fluid status and fluid
responsiveness can also be assessed in mechanically ventilated patients by
means of the superior vena cava collapsibility index (TEE bicaval view) or
inferior vena cava distensibility index (TTE subcostal view). In addition,
echocardiography allows the rapid and reliable estimation of SV. Finally, there
are particular and specific conditions in which diagnosis and treatment are
strictly related to the echocardiographic examination (e.g., pericardial effusion,
valve disruptions, aortic dissection, and systolic anterior motion of the mitral
valve).
A miniaturized, disposable monoplane TEE probe that can be left in place for
up to 72 h (ClariTEETM, ImaCor Inc., Garden City, NY) has recently been
introduced and has the potential to provide ongoing qualitative cardiac
assessment.
We believe that where expert echocardiography skills are not available, then
training programs should be developed to ensure that clinicians taking care of
the high-risk patient are familiar with at least the basic applications of TTE and
TEE.
Echocardiography has become an indispensable tool in the evaluation of
medical and surgical patients. As ultrasound (US) machines have become more
widely available and significantly more compact, there has been an exponential
growth in the use of transthoracic echocardiography (TTE), transesophageal
echocardiography (TEE), and other devices in the perioperative setting. Here, we
review recent findings relevant to the use of perioperative US, with a special
focus on the hemodynamic management of the surgical patient.
In an attempt to make hemodynamic monitoring less invasive and to acquire
additional relevant information not obtained with other monitoring approaches,
ultrasound (US) devices are increasingly being used in perioperative medicine
[1]. The field is rapidly evolving as technology advances. Here, we describe the
basic principles of ultrasonography and how it can be used for hemodynamic
monitoring in the perioperative setting.
TTE and TEE allow the differentiation between noncardiac and cardiac
causes of hemodynamic instability. Valvular pathologies and abnormalities in
ventricular function can be assessed. During noncardiac surgery, the American
Heart Association (AHA) and the American College of Cardiology (ACC)
recommend the use of echocardiography in the “evaluation of acute, persistent
and life-threatening haemodynamic disturbances in which ventricular function
and its determinants are uncertain and have not responded to treatment” [41].
10.4.1 Ventricular Function

Global, systolic LV function can be visually estimated. According to current
SCA recommendations, this basic qualitative assessment is not precise, but
sufficient for the identification of patients who might benefit from inotropic
therapy [12]. The SCA recommends using the transgastric (TG) mid-papillary
short-axis (SAX) view, as well as the mid-esophageal (ME) four-chamber, the
ME two-chamber, and the MOE long-axis (LAX) views for the monitoring of
LV function.
10.4.2 Intravascular Volume Status
Hypovolemia is a common cause of cardiocirculatory instability in the operating
theater and the intensive care unit. A central concept in the care of critically ill
patients and patients undergoing surgery is to predict fluid responsiveness: Will a
patient’s hemodynamic situation improve (i.e., increase in SV and CI) with fluid
administration or not? If certain preconditions are met (closed chest, controlled
ventilation with sufficiently high tidal volumes, regular heart rhythm, and
normal intra-abdominal pressure), systolic pressure variation (SPV), arterial
pulse pressure variation (PPV), and stroke volume variation (SVV) represent
“dynamic” parameters that more reliably predict fluid responsiveness. CVP and
LV end-diastolic area (EDA) do not predict fluid responsiveness, as they are
static parameters that are dependent not only on volume status. Other variables
impacting CVP and LV-EDA include cardiac compliance (i.e., diastolic
ventricular function) as well as intrathoracic pressure. Consequently, LV-EDAI
(LV-EDA indexed to the body surface area) does not correlate with fluid
responsiveness. Other studies confirmed the inferiority of LV-EDA in predicting
fluid responsiveness in comparison to dynamic parameters. Different systematic
reviews also concluded that LV-EDA is inferior compared to dynamic
parameters such as PPV.
10.4.3 Valvular Function

For a basic assessment of valvular regurgitation, visual inspection of the
regurgitant jet area, vena contracta width, as well as flow reversal in receiving or
originating cardiovascular chambers can be used among other criteria. Stenotic
lesions can be grossly evaluated by continuous-wave Doppler using an imaging
plane parallel to blood flow (see the Doppler section above). An orienting
assessment of valvular function should be part of every basic echocardiographic
examination.
10.4.4 Pulmonary Embolism, Pericardial Effusion, and

Thoracic Trauma
Hemodynamically relevant pulmonary embolism (PE) is one reason of
cardiocirculatory compromise. In the intraoperative or emergency setting, TOE
might be the only feasible yet reliable tool to detect the presence of
hemodynamically relevant emboli. Signs of RV failure and motion abnormalities
of the RV free wall permit the diagnosis of PE in patients with hypotension or
shock.
The modern approach to the hemodynamic evaluation including the
TTE/TEE evaluation is a part of the anesthetist skill [42].
10.5 Fluid Management and Functional Hemodynamic

Monitoring
Inadequate fluid management may lead to reduced CO and DO2 to injured
tissues, which is associated with an increased incidence of postoperative
complications [43]. Moreover, the systemic inflammatory response associated
with tissue injury results in capillary leak and tissue edema (Fig. 10.2). Fluid
restriction and diuresis may decrease edema in patients with poor ventricular
function but may also increase the incidence of acute kidney injury. Meanwhile,
excessive fluid administration may lead to a range of adverse effects including
coagulopathies and edema of the lungs, gut, and peripheral tissues (Fig. 10.2).
Retention of sodium and water following surgery may reduce requirements for
fluids. Once the patient is stabilized, additional amounts of fluids should only be
given to correct deficit or continuing losses. Unfortunately, estimates of fluid
deficit based on traditional physiological parameters, such as heart rate, blood
pressure, and cardiac filling pressures, are not sufficient.
Fig. 10.2 Periop fluid and HD management. HSR high risk surgery, Pts patients, HD hemodynamic, Hb
hemoglobin
10.5.1 Static Indicators of Preload

CVP: Many high-risk surgical patients have a CVC in place and a CVC is a
requirement for some devices needing calibration by thermodilution.
Despite its limitations (vide supra), changes in CVP over time may be
helpful to guide fluid therapy, especially when it is low and associated with
low flow. A CVP >8 mmHg might also be considered as an “alarm” for
potential venous congestion associated or not with fluid overload [15].
GEDV/ITBV and EVLW: These are volumetric parameters derived from
transpulmonary thermodilution and are integrated into the PiCCOTM plus,
PiCCO2 TM, and EV1000TM monitors. EVLW can help in the identification
of (cardiogenic or non-cardiogenic) pulmonary edema and has the potential
to increase the safety of fluid therapy in patients with structural lung
disease, ARDS, or congestive heart failure.
The end-diastolic area of the left ventricle may be the most reliable static
parameter of preload, but is largely dependent on LV diastolic compliance.
Its ability to accurately predict fluid responsiveness is limited.
10.5.2 Functional Hemodynamic Parameters

Positive pressure ventilation induces cyclical changes in intrathoracic pressure,
which affect preload by decreasing venous return to the right heart and
increasing venous return to the left ventricle. The degree of the resulting changes
in LV SV (SVV) and pulse pressure (PPV) better predict fluid responsiveness
than do static parameters, when RV function is not a limitation and for a fixed
tidal volume. Most devices using pulse contour analysis, including the current
version of the noninvasive ClearSight monitor, display SVV and PPV. Despite
the numerous validity criteria required to interpret such variations, these
variables may help predict fluid responsiveness at different thresholds and have
been integrated into hemodynamic optimization protocols [44].
Respiratory variations in the pulse oximeter plethysmographic waveform
(∆POP) have been shown to predict fluid responsiveness in mechanically
ventilated patients, similar to changes in the arterial pressure waveform [45].
The MasimoTM (Masimo Corp., Irvine, California, USA) device provides
automated calculation of the pleth variability index (PVI) by measuring changes
in perfusion index over a time interval including at least one complete
respiratory cycle. The PVI has been shown to predict fluid responsiveness in
various perioperative settings and has been integrated into fluid optimization
algorithms. However, the PVI has the same limitations as the other dynamic
parameters and has limited accuracy in the presence of vasoconstriction with or
without the use of vasopressors [46–48].
Today, we can recommend that dynamic parameters be used as an integral
part of GDT protocols. The limitations of each dynamic index must be taken into
consideration as well as the concept of a gray zone. Dynamic parameters neither
provide a measure of fluid bolus effectiveness nor should they be used as an
indication to give fluids. The final decision to administer fluids must be
supported by the apparent need for hemodynamic improvement, the presence of
fluid responsiveness, and by the lack of associated risk.
We recommend crystalloid solutions for routine surgery of short duration.
However, in major surgery, the use of a goal-directed fluid regimen containing
colloid and balanced salt solutions is recommended. Though a black box
warning for the use of starch solutions exists within the United States, there is
limited data relative to their harm in the perioperative space. Careful
consideration should occur in patients with known renal dysfunction and/or
sepsis prior to administering starch solutions [43].
10.5.3 Limitations
It is important to note that all the dynamic variables have significant
confounding factors [44]. The reliability of these indices is affected by
spontaneous breathing activity, arrhythmias, right heart failure, decreased chest
wall compliance, and increased intra-abdominal pressure, although most of these
limitations are uncommon in the OR. Nevertheless, in the ICU a relatively small
proportion of patients present suitable criteria for these indices [49]. Another
major limitation of dynamic parameters is that they are dependent on the size of
the tidal volume. Some authors have suggested that they require a tidal volume
of at least 8 ml/kg body weight [50], although they have been successfully used
with tidal volumes of 6–8 ml/kg body weight [47, 48]. A recent study and meta-
analysis have indicated a decreased rate of postoperative complications when
low tidal volumes are applied during anesthesia [51, 52], and increased use of
protective ventilation (lower tidal volumes) in the OR may reduce the usefulness
of dynamic parameters or at least require new interpretation rules. Finally, within
a range of PPV values of 9–13 %, fluid responsiveness cannot always be reliably
predicted; there is a “gray zone” in which prediction of fluid responsiveness is
difficult. One study [53] indicated that fluid responsiveness could not be reliably
predicted using dynamic measures in as many as 25 % of anesthetized patients.
A passive leg raising (PLR) test has been suggested to overcome some of
these limitations in dynamic evaluation, but should be performed rigorously with
simultaneous analysis of continuous CO monitoring. It is obviously impractical
during most operative conditions [54]. In addition, the blood volume shift from
the leg to the central compartment is non-predictable. In a hypovolemic state, it
is reasonable to consider a volume shift less than that generated in “normal”
volemic conditions.
Despite these limitations and confounding factors, whenever possible, one is
advised to assess fluid responsiveness using the available functional
hemodynamic parameters before attempting to increase CO with fluid
administration. This approach can indicate if and when CO can be further
increased by fluids, and identify when the flat portion of the cardiac function
curve has been reached, thus preventing unnecessary fluid loading [44]. It is also
important to remember that, generally speaking, fluid responsiveness is not an
(absolute) indication to give fluids. Decisions about fluid administration should
not be based only on dynamic parameters but also on the likely risk associated
with fluid administration. During surgery, systematic fluid administration in the
presence of fluid responsiveness may improve postoperative outcomes [55].
10.6 Venous Oxygen Saturation

Changes in SvO2 may reflect important pathophysiological changes in the
relationship between DO2 and VO2, both of which may fluctuate significantly
during the perioperative period.
Reorganization of the Fick equation shows that
From this equation, it is clear that SvO2 will decrease in the presence of
hypoxemia, hypermetabolic states (increased VO2), a decrease in CO, or anemia.
Changes in SvO2 are therefore directly proportional to those in CO, only when
SaO2, VO2, and hemoglobin concentration remain constant. The normal SvO2 in
health is around 75 %, but it is closer to 70 % in acutely ill patients who have a
somewhat lower hemoglobin concentration.
Central venous oxygen saturation (ScvO2) from a central venous catheter is
used as a surrogate for SvO2 when a PAC is not in situ, with some limitations.
Although the determinants of ScvO2 and SvO2 are similar, they cannot be used
interchangeably [56]. Regional variations in the balance between DO2 and VO2
result in differences in the hemoglobin saturation of blood in the superior and
inferior vena cava. ScvO2 is affected disproportionately by changes in the upper
body and does not reflect the SvO2 of coronary sinus blood. In healthy
individuals, ScvO2 may be slightly less than SvO2, because of the high oxygen
content of effluent venous blood from the kidneys, but this relationship is
reversed during periods of hemodynamic instability as blood is redistributed to
the upper body at the expense of the splanchnic and renal circulations. In shock
states, therefore, ScvO2 may exceed SvO2 by up to 20 %. This lack of
equivalence has been demonstrated in various groups of acutely ill patients
including not only those with shock but also in patients undergoing general
anesthesia for cardiac and noncardiac surgery. Even trends in ScvO2 do not
closely reflect those of SvO2 [57–59].
Lower values of ScvO2 have been associated with more complications in
patients undergoing cardiothoracic surgery. Some authors have proposed to
maintain SvO2 or ScvO2 above a cutoff value. In patients undergoing elective
cardiac surgery, administration of intravenous fluid and inotropic therapy to
attain a target SvO2 ≥ 70 % in the first eight hours after surgery was associated
with fewer complications and a shorter hospital stay. In patients undergoing
major abdominal (including aortic) surgery, achieving an oxygen extraction ratio
of less than 27 % (from intermittent measurements of ScvO2) was associated
with a shorter hospital stay [57, 58].
During surgery this measurement is less informative: Firstly, hypoxemia is
generally corrected; secondly, under anesthesia, especially with neuromuscular
paralysis, oxygen use decreases in all tissues, so that reductions in ScvO2 are
uncommon. Nevertheless, low ScvO2 values imply first and foremost that CO
may be inadequate. At the same time, very high ScvO2 values may imply that
oxygen extraction is low, purporting a worse prognosis, at least during cardiac
surgery [59].
10.7 Blood Lactate Concentrations

Lactate is a physiological substrate (carbohydrate) produced from pyruvate
reduction during cytosolic glycolysis. In stable conditions, lactate production
and elimination are equivalent, i.e., 1200–1500 mmol per day, leading to a stable
blood lactate concentration of 0.8–1.2 mmol/L. The net flux of lactate depends
on the difference between release and uptake and varies among organs and with
their energetic conditions [60]. Hyperlactatemia is associated with increased
morbidity and mortality in critically ill patients [61–64]. Persistent
hyperlactatemia is a more relevant indicator of poor outcome than an isolated
elevated lactate value. Hyperlactatemia is not always a consequence of tissue
hypoxia, but also of an accelerated “aerobic” glycolysis resulting from cytokine
influence and catecholamine stimulation, a situation termed “stress
hyperlactatemia.” In practice, irrespective of the different metabolic
modifications, an elevated lactate level indicates the presence of shock, and a
decrease in lactate levels over time is a good indicator of effective treatment.
Accordingly, repeated blood lactate measurements are recommended to monitor
lactate production and clearance over time during surgery in high-risk patients.
10.8 Management Strategies Based on Perioperative

Monitoring
There is good evidence that the use of flow-based hemodynamic monitoring
combined with hemodynamic manipulation in the perioperative period can
reduce morbidity and sometimes mortality [65–71]. For a variety of reasons,
however, this approach has not been adopted everywhere and has even been
challenged [72]. Indeed, there have been some important problems with many
clinical trials in the field, such as lack of blinding and suboptimal management
of the control group.
There are basically two options to optimize perioperative cardiovascular
management, both of which aim to increase SV/CO by means of fluid loading
(increase in cardiac preload) and/or inotrope administration (increase in
contractility):
(a) One is reactive, by applying a rapid intervention only when a

hemodynamic change occurs. One should then individualize treatment with
fluid challenge techniques. The response to the rapid administration of a
fluid bolus (e.g., 150 ml) can be evaluated during surgery (especially in the
presence of signs of fluid responsiveness). The response can be monitored
by evaluating the blood pressure or heart rate but the CO/SV response is
much more accurate. Inotropic agents are added in the absence of an
adequate response. Reactive approach includes:
Correct hypotension and tachycardia.
Give fluids in the presence of suspected hypovolemia with increased
pulse pressure variation (PPV), systolic pressure variation (SPV),
stroke volume variation (SVV), or pleth variability index (PVI).
Identify a reduction in cardiac output (CO) and react promptly with
fluid challenge.
Identify a reduction in central venous oxygen saturation (ScvO2) and
react promptly with fluid challenge.
(b) The other chance is proactive, based on a strategy of hemodynamic

manipulation targeting supranormal CO or DO2 values to minimize the risk
of tissue hypoperfusion. Adequate fluid administration is the first element
of this strategy. Several studies have indicated that fluid management based
on PPV, SVV, and SV optimization may decrease postoperative wound
infections and possibly postoperative organ dysfunction [73, 74]. Inotropic
agents may be added if fluids alone are not sufficient for this purpose.
There is a risk of overtreatment as excessive use of dobutamine has been
associated with increased rates of complications [75]. The use of
dopexamine as an alternative has given controversial results [76, 77].
Proactive approach includes:
Maintain arterial pressure and heart rate within acceptable ranges.
Maximize stroke volume (SV).
Maintain PPV or SVV < 12 % or PVI < 14 %.
Maintain cardiac index (CI) or oxygen delivery (DO2) in a desired
range (e.g., CI > 4.5 L/min.M2, DO2 > 600 mL/min).
Maintain ScvO2 > 65 %.
The algorithms should be used as part of the perioperative fluid plan. These
should be available and easily accessible within all operating rooms, PACU, and
ICU (Fig. 10.3). Clinical needs, invasiveness, accuracy, and precision of
available technologies should be considered when selecting monitoring devices.
Fig. 10.3 Perioperative fluids and GDT “tailored”
While the benefits of perioperative goal-directed fluid therapy have yet to be

proven, the bulk of clinical research supports the implementation of a step-by-
step GDT plan and an appropriate HD monitoring (Fig. 10.4) which is to begin
in high-risk surgical patients immediately after induction of anesthesia until the
first postoperative hours. First, determine if the patient requires hemodynamic
support or augmentation of cardiovascular function. Second, if the need is
apparent and the patient is fluid responsive, fluid bolus therapy should be
considered and guided by continual, and if available continuous, assessment of
fluid responsiveness as described below and to continue for the first six
postoperative hours.
Fig. 10.4 A step-by-step approach to the appropriate HD monitoring
Bolus therapy rather than continuous infusion when the goal is to improve
pressure, perfusion, and oxygen delivery is recommended. Standardization of the
fluid bolus relative to fluid composition, volume, infusion rate, and time to post-
bolus assessment should be implemented. The variables used for assessing the
effectiveness of the fluid bolus should include appropriate changes in cardiac
output or stroke volume (Fig. 10.3, 4).
Conclusions
Hemodynamic monitoring systems play an important role in optimizing
perioperative hemodynamic management.
The new HD monitoring devices implement the classical one, but the use
of hemodynamic monitoring devices per se in the perioperative setting has
not been shown to be associated with improved outcomes. However,
appropriate measurement and interpretation of cardiovascular variables may
help guide therapeutic interventions, which could improve patient outcomes.
The most appropriate system must be selected for the individual patient prior
to surgery, taking into consideration the individual risks of the patient and the
procedure. Appropriate interpretation of the information offered by
hemodynamic monitoring requires the integration of several variables. The
PAC still represents the goal standard for the PA pressure monitoring and for
all the very critically ill patients. The mini-invasive CO monitoring systems
are very useful tools in the OR and in all those intermediate-risk patients
undergoing major surgery. Echocardiography is increasingly used as a first
tool to identify a problem and help select initial treatment. To improve patient
management and outcome, the clinician must understand the advantages and
the limitations of the various tools and parameters used during perioperative
care.
Although perioperative fluid management remains a highly debated
subject, data suggests that goal-directed fluid therapy with the objective of
hemodynamic optimization can reduce complications after major surgery.
Specific hemodynamic goals include maintaining adequate circulating
volume, perfusion pressure, and oxygen delivery.
In summary, fluids should be treated as any other intravenous drug
therapy; thus, careful consideration of its timing and dose is mandatory. A
perioperative fluid plan should be developed which is easily understood and
used by all anesthesiologists within a group, facility, or healthcare system.
Determining both the need for augmented perfusion and fluid responsiveness
is fundamental when making fluid therapy decisions to avoid unjustified fluid
administration. The use of algorithms as part of the perioperative fluid plan is
recommended.
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DOI 10.1007/978-3-319-19908-5_11
11. What Are the Specific Challenges in the

Postoperative Mechanical Ventilation After
Thoracic Surgery?
Edmond Cohen1, Peter Biro2 and Mert Şentürk3
(1) Departments of Anesthesiology and Thoracic Surgery, The Icahn School of
Medicine at Mount Sinai, New York, NY, USA
(2) Institute of Anesthesiology, University Hospital Zurich, Zurich, Switzerland

Mert Şentürk
Email: senturkm@istanbul.edu.tr
11.1 Introduction
The incidence of mechanical ventilation for more than 48 h after thoracic
surgery has been reported to be necessary in up to 9.3 % [1]. It is also well
known that the requirement and also the duration of mechanical ventilation after
thoracic surgery are significantly correlated to postoperative morbidity [2, 3].
Although these figures in older publications appear to be unrealistically high for
current practice, it has to be kept in mind that thoracic surgery and anesthesia
deal with patients with more morbidities than 20 years ago. Moreover, even if
the incidence of problems might not be higher, the intensity of the challenge
remains the same. In a recent meta-analysis, it has been demonstrated that the
incidence of postoperative “acute lung injury” (ALI) after thoracic surgery was
4.3 %. Although this rate was similar to the one of the abdominal surgery (3.4
%), the attributable mortality of postoperative lung injury was higher in patients
after thoracic interventions (26.5 % vs 12.2 %) [4].
Other chapters in this book cover some topics of this chapter too, such as the
ICU indications after thoracic surgery, how to predict and protect postoperative
respiratory failure, as well as noninvasive ventilation and extracorporeal lung
assist. This chapter will focus therefore on some specific challenges of
mechanical ventilation in postthoracotomy patients.
11.2 Ventilatory Support After Thoracic Surgery

Thoracic surgery is unique in the sense that the target organ of both the surgery
and of mechanical ventilation is the same. Not only may surgeons remove large
parts of the lungs, they often traumatize parts of the remaining healthy lung
tissue, and they also may damage the respiratory muscles. Moreover,
thoracotomy is one of the most painful incisions which can further impair
ventilation. One can assume that the postoperative lung injury would be more
likely due to the surgical trauma. However, it has been shown that the degree of
radiological density increase was significantly greater in the nonoperative lung
compared to operative lung after lobectomy [5].
Almost all complications (both respiratory and non-respiratory) after thoracic
surgery result in respiratory failure (Fig. 11.1). The clinical picture is usually a
mixed one rather than pure hypoxemic or pure hypocapnic:
Fig. 11.1 CT scan of a patient who developed adult respiratory distress syndrome after thoracotomy. CT
scan of a patient following thoracotomy for left upper lobectomy who subsequently developed adult
respiratory distress syndrome: There is space where the lung tissue was resected, atelectatic areas in the
remaining lung tissue, infiltrations in both lungs without any clinical signs of infection, and subcutaneous
emphysema
A reduced functional lung volume may result from resection of

parenchyma, atelectasis, lung edema, and thoracic restriction from
postoperative pain.
Decreased functional residual and volume capacities, dysfunction of the
diaphragm and intercostal muscles, and increased airway resistance may
cause impaired ventilation.
Ventilation-perfusion mismatch and decreased minute ventilation may lead
to impaired gas exchange [6].
In addition, excessive intravenous fluid infusion and blood transfusion can
directly harm or exacerbate harm to the lungs.
Actually, mechanical ventilation in the PACU or ICU should be avoided if
possible, since it can cause a “ventilator-associated or ventilator-related lung
injury” or worsen it. Every attempt of invasive mechanical ventilation is
associated with a risk of making things worse while trying to improve the
patient’s condition. This risk is higher in patients after thoracotomy because the
lungs (both the operated and the ventilated lung) have already been exposed to a
“first hit” during the operation. In addition, clinical experience would suggest
that positive pressure ventilation can injure fresh anastomoses or bronchial
stump, although there is no evidence for this plausible assumption.
11.3 Practical Hints

Pragmatic rules that would help to decrease the possibility of having
unwarranted events when deciding to continue mechanical ventilation after
thoracic operations:
On the one hand, anesthesiologists, surgeons, and intensivists have to avoid
postthoracotomy mechanical ventilation. On the other hand, the longer the
patient has to deliver an increased work of breathing, the later he will
recover from respiratory failure.
Spontaneous breathing is better than mechanical ventilation, and assisted
ventilation is better than controlled one. However, the need for tracheal re-
intubation can be considered as a worst case scenario.
The decision to ventilate should be made intraoperatively, and preoperative
predictions should be continuously reevaluated.
If mechanical ventilation needs to be continued, the intraoperative double-
lumen tube (DLT) should be replaced at the end of surgery with a normal
single-lumen tracheal tube. However, in patients who are intended to be
extubated within two hours postoperatively, the DLT may remain in place
with a deflated bronchial lumen cuff.
Transition to a single-lumen tube should be performed via a tube exchanger
of sufficient length (caveat: DLTs are longer than single-lumen tubes). It
should be kept in mind that an “easy” intubation at the start of the operation
may later become “difficult” due to various reasons such as airway edema.
In a patient, in whom postoperative ventilation is planned, the use of a
bronchial blocker (BB) can be indicated because this avoids the transition
from the double- to a single-lumen tube. Thus, the BB has to be removed
only.
A Univent® tube (LMA North America Inc, San Diego, CA) can remain in
place for postoperative ventilation, but the blocker should be pulled back
into the main lumen.
Finally, weaning from mechanical ventilation is a process that should start
on admission of a patient to ICU whose trachea is intubated.
11.4 Protective Lung Ventilation

Actually, the concept of “protective lung ventilation” (PLV) was defined and
determined in ARDS patients [7], but this approach becomes even more
important in the vulnerable lungs of patients after thoracic surgery. PLV
includes:
Low tidal volumes (TV) of 6–8 ml/kg
Appropriate positive end-expiratory pressure (PEEP)
Recruitment maneuvers (RM)
Meta-analyses have found PLV to be effective and protective in both ARDS
in the ICU and in OLV [8–10]. An intraoperative TV of 6–8 ml/kg has been
associated with a decreased frequency of postoperative pulmonary failure [11].
Although there is no evidence that the same argument is also valid for the
postoperative period, there is clear evidence for using these guidelines in general
ICU patients. Moreover, this circumstance means to have a reduction of
functional lung tissue that is similar to the “baby lung” in ARDS [12].
The details of this strategy are extensively discussed elsewhere in this book;
the authors will only focus on some recent dilemmas:
1. Is any particular component “more” important than the other? Recently, it

has been reported that the driving pressure (defined as TV/respiratory
system compliance) (DP) is the ventilation variable that best classifies as a
risk of ALI in ARDS patients [13]. Changes in DP play a much more
important role as compared to PEEP or peak inspiratory pressure (PIP). It is
questionable, whether it is more appropriate to define the PLV with “low
DP” (of less than approximately 20 cmH2O) rather than “low TV.”
2. Is a TV of 6 mL/kg protective enough? Considering that thoracic surgery is

usually associated with a reduction in lung volume, e.g., in a patient after
pneumonectomy, 6 mL/kg would mean again to be too high and maybe not
protective anymore. In an animal study, applying the same TV to one lung
compared with two lungs has resulted in significantly greater lung injury
shown in histologically assessed “diffuse alveolar damage” score [14]. On
the other hand, halving the TV to 3–4 mL/kg, its size would decrease below
dead space ventilation. Empirically, a TV of 4–6 mL/kg seems rational, but
needs to be proven and checked on an individual basis.
3. What if the DP is still high even if TV is kept low? In cases of severely

decreased lung compliance and/or severe reduction effective lung volume,
very high driving pressures can be necessary even for low TVs. Although it
is a very rare condition, the so-called ultraprotective ventilation (application
of extracorporeal lung assist (ECLA) systems) might become necessary. It
has been shown in two studies (an animal study [15] and a clinical study
[16]) that ECLA helps to decrease the TV to very low amounts to avoid high
pressures during ALI in the postoperative period. The resulting survival rate
was much higher than in the conventional setting (100 % in the animal study
and 86 % (six of seven patients) in humans). ECLA is discussed in another
chapter in this book.
4. “How to apply ‘PEEP’?” PEEP is “good” not only for the improvement of
oxygenation but also (and maybe more importantly) for the improvement of
the V/Q relationship in the dependent lung and for prevention of alveolar
collapse at end expiration by increasing the functional residual capacity
(Fig. 11.2) [17]. However, excessive PEEP can also lead to an unnecessary
and harmful rightward shift of the ventilation in pressure-volume curve (Fig.
11.3). Moreover, although it is not evidence based and may even sound
irrational, “clinical experience” would suggest that positive pressure
ventilation can injure fresh anastomoses or bronchial stumps. An approach
to keep PEEP “as high as necessary” and “as low as possible” can help to
overcome both atelectasis and alveolar overdistension [18]; but practically,
this issue is more complicated than at first sight. A “decremental trial”
following a recruitment maneuver (RM) (stepwise decline of PEEP from 20
cm H2O) to adjust the best compliance appears to be appropriate [19].
Fig. 11.2 Relationship of FRC (functional residual capacity) and CC (closing capacity) in different
ventilatory settings. Right: FRC falls below CC during mechanical ventilation; a larger tidal volume
(TV) can obtain a better gas exchange (note the larger area above the CC line); however, a cyclic
recruitment cannot be avoided. Left: Applying PEEP during keeping the TV low: PEEP obtains an
FRC above the CC. Cyclic recruitment is avoided; and the ventilation (now the area above the “new”
FRC) is still better than the one without PEEP (Adapted from [17] (with permission))
Fig. 11.3 Relationship of PEEP and LIP (lower inflection point). Note that LIP can differ in each
individual and can sometimes be zero. A, B, and C are possible points for total (intrinsic + external)
end-expiratory pressure. The level of external PEEP should be adjusted to get closer to LIP, e.g., if the
external PEEP brings the total PEEP from A to B, oxygenation gets better, but if the external PEEP
brings the total PEEP from B to C, oxygenation gets impaired; if the LIP is 0, the best oxygenation is
obtained by A (Adapted from [17] (with permission))
5. How to recruit? While PEEP can keep the lung open, it is not capable of
opening an atelectatic lung. To open collapsed regions, a recruitment
maneuver (RM) is necessary [20]. However, in patients with air leak, RM is
contraindicated; moreover, in patients without an air leak (or with a small
one), there is a common “fear” of the high pressure generated by RM, and
PEEP may disrupt bronchial stumps and anastomoses. RM after thoracic
surgery is an issue, of which pros and cons have to be examined in the
individual clinical setting.
11.5 Permissive Hypercapnia

Clinicians tend to compensate the reductions in TV by an increase in frequency
to maintain the minute ventilation volume. However, this might be wrong:
1. The price of shorter inspiration can be a higher airway pressures, and the
consequence of shorter expiration can be air trapping and auto-PEEP.
2. Physically, it is the “power” that plays a role in the lung injury (rather than
“work”), and therefore “the number of the hammer hits per time” is also
important (quote of Luciano Gattinoni). Increasing the respiratory rate (=hits
with the hammer) increases the energy that causes the lung injury.
3. More importantly, mild hypercapnia is not only something that can be

permitted in many cases [21], it can also be even therapeutic for several
hours [22]. Permissive hypercapnia may protect the lung and improve the
tissue oxygenation as a result of the increased cardiac output and the
resulting right shift of the oxygen (O2) saturation curve [23].
4. On the other hand, it should be kept in mind that hypercapnia exacerbates

hypoxic pulmonary vasoconstriction, and therefore, it is contraindicated in
pulmonary hypertension, which is more frequent in patients after
thoracotomy. In the remaining population, permissive hypercapnia can be
considered as a standard procedure of protective lung ventilation.
11.6 Inspired Oxygen Fraction

Increased O2 consumption in postoperative patients has led to a routine
administration of supplemental O2. However, it has been shown that this
approach could be more harmful than beneficial [24]. Although this study was
performed in medical emergencies, the mechanism of the damage from high
FiO2 can be viewed as valid for patients after thoracic surgery. These are the
postulated pathways of possible damages caused by hyperoxia:
1. Coronary and systemic vasoconstriction leading to a decreased stroke

volume.
2. Even a short period of preoxygenation with an FiO2 of 1.0 can lead to

atelectasis as a result of collapsed alveoli because of the replacement of
nitrogen [25].
Obviously, hypoxemia of the postoperative patient should be treated, but one
still has to avoid hyperoxia: Hypoxemia should be treated with stepwise
increases in FiO2 as high as necessary to avoid hyperoxia [24].
Recently, increasing the FiO2 prior to application of the bundle of “low TV-
PEEP-RM” has been advocated: the so-called permissive atelectasis. Although
this suggestion was limited to mechanical ventilation during anesthesia of the
“healthy” lungs, the extrapolation to postthoracotomy patients should be
examined [18].
11.7 Ventilation Mode

Considering that it is the “driving pressure” (DP) that is the principle reason for
lung injury, it appears to have less or even no meaning whether to apply the
same DP with pressure-controlled (PCV) or volume-controlled way (VCV).
Previous studies advocating PCV because of its “descending flow pattern” that
resembles more to physiologic spontaneous breathing in OLV [26] have not been
confirmed in more recent studies with similar settings [27]. The effects during
postoperative period can be considered to be similar.
The only difference between these ventilation modes is probably the lower
peak (not the plateau) airway pressures, which contributes less (if any) to ALI.
Recently it has been shown in OLV that PCV was more associated with an
improvement in right ventricular function than VCV.[28] Right ventricular
function is crucial for patients after thoracic surgery; however, whether the
reported advantage can also be extrapolated for the postoperative period also
remains to be examined.
Physiological breathing is irregular in all its components (TV, frequency,
sighs, etc.). It has been shown in an experimental ALI study that a so-called
“noisy” pressure support ventilation was associated with an improvement in
oxygenation and also a redistribution of pulmonary blood flow [29].
11.8 Patients Requiring Mechanical Ventilation, but

Having a Leak
The most “specific” challenge of postthoracotomy mechanical ventilation
appears to be the patients with a persisting air leak and a need of mechanical
ventilation. Both conditions deteriorate each other: persisting air leak aggravates
the respiratory failure and increases the need for mechanical ventilation, and
positive pressure ventilation sustains and aggravates the air leak. In these
patients, noninvasive ventilation can be tried (which is discussed in another
chapter). In some cases, application of high-frequency jet ventilation or
differential lung ventilation can be necessary.
11.9 High-Frequency Jet Ventilation (HFJV) After
Thoracic Surgery
High-frequency jet ventilation (HFJV) plays a marginal role in the postoperative
ventilation after thoracic surgery since it has only one rational indication: the
presence of a bronchopleural fistula [30]. It’s a basic characteristic of jet
ventilation in general that it usually produces lower positive airway pressure
than conventional ventilation. This is due to the circumstance that HFJV is only
possible if the airway is kept open to the atmosphere to enable free air egress.
This way, a positive airway pressure cannot build up, except when the exhalation
pathway is blocked. In the case of a bronchopleural fistula, there are even two
separate openings that permit the efflux of gas: (1) the proximally open upper
airway (e.g., via a tracheal or bronchial tube) and (2) via the fistula. Air egress
through the fistula is nevertheless an undesired effect, since it prevents closure
and healing of the pathology. Therefore, it is the goal of the therapy that this
pathway should occlude as soon as possible by minimizing the gas flow. This
might be facilitated by a lower airway pressure, than it would occur during
conventional ventilation. Additionally, a large amount of gas loss through the
fistula would even impede the application of positive pressure ventilation. These
circumstances lead to the consideration of HFJV as a better means to ventilate
the affected lung if a unilateral single-lung ventilation of the dependent lung is
considered insufficient to maintain gas exchange. Usually, the bronchopleural
fistula is unilateral and may occur on the side of the preceding lung surgery. If
the leak caused by the fistula is small, spontaneous breathing should be
maintained, since this way the airway pressure is also very low. However, if
ventilator support is considered necessary, a differential ventilation of the two
lungs should be considered.
During the operation, the airway was intubated with a double-lumen tube. If
the fistula becomes apparent after extubation, and it attains a magnitude that
requires ventilator support, the most feasible interface to apply ventilation would
be again a double-lumen tracheal tube in order to separate the two lungs. The
primary scope of lung separation is to permit conventional ventilation of the
healthy lung, while the affected one will receive HFJV [31, 32].
The settings of HFJV for the affected lung may be adjusted according to the
metabolic needs of the patient. The goal is to apply as much HFJV as necessary
(to maintain an adequate gas exchange) and to reduce it to the lowest possible
extent (to obtain the lowest possible gas loss through the fistula). The main
determinant of the amount of HFJV is driving pressure (DP), which leads to
resulting parameters such as gas flow, tidal volume, and airway pressure. It’s
absolutely necessary to titrate the DP stepwise to the magnitude which is optimal
in the mentioned sense. This setting has to be readjusted regularly to changes in
the size of the gas leak. Other settings are oxygen concentration, inspiration
duration, and frequency. Oxygen concentration should be set according to the
resulting oxygenation parameters; the inspiration duration is of secondary
importance and should be set at 40 or 50 %, while the ventilation frequency may
be variated between 120 and 300 cycles per minute. The choice of the frequency
should allow for the lowest possible airway pressure by choosing a high
frequency, while an eventually necessary contribution to carbon dioxide
elimination might require a low frequency; in this respect an ideal balance
between these two interests should be found. In most cases one would begin
HFJV with 100 % oxygen, a DP at 1.5 bar, inspiration duration of 40 %, and a
frequency of 150 cycles per minute. The resulting blood gases may indicate the
moment when the DP may be stepwise lowered as well as the frequency may be
increased. This development would represent the desired healing of the
underlying pathology. As soon as one arrives at a DP < 0.8 bar and a frequency
of 300 cycles per minute, the contribution of HFJV to oxygenation and carbon
dioxide elimination becomes small and might be discontinued. This also would
allow abrogating lung separation and ventilator support.
11.10 Differential Lung Ventilation

For a thoracic anesthetist, differential lung ventilation (DLV) appears to be
familiar as a variant of OLV. For patients after thoracic surgery, DLV has two
major indications: unilateral lung processes and air leaks [33]. The rationale is to
ventilate both lungs – synchronized or not – with different TVs and/or PEEPs. In
ARDS, this method has been used primarily in unilateral pathologies; however,
it can be used also successfully in bilateral ARDS in lateral decubitus position,
where the heterogeneous distribution of ventilation can be divided to both lungs
via the decubitus position; in this manner, DLV enables the titration and
application of “selective optimal PEEPs” to both lungs [34].
The aim of DLV in a patient with air leak/fistula is to promote healing in the
sick lung with a very modest DP while compromising less severely oxygenation
and gas exchange. It can also protect the healthy lung against the pathologic
processes of the other lung including massive unilateral hemoptysis,
bronchiectasis, and lung abscesses.
During DLV, two coupled ventilators (“master” and “slave”) with
synchronized inspiration and expiration can be used. Two ventilators can also be
used in an asynchronized manner, but this may cause a mediastinal shift. The
“healthy” lung is ventilated with conventional setting (to take over the gas
exchange); the lung with the leak is ventilated with very less TV, lower or no
PEEP, and never recruitment maneuvers.
An easier solution is to ventilate one lung (the “healthy” one) with the
conventional setting, while continuous positive airway pressure (CPAP) or high-
frequency ventilation (HFV) can be applied to the “sick” lung (Fig. 11.4).
Fig. 11.4 In a patient with persistent bronchopleural fistula requiring mechanical ventilation, the lung (or
the lobe) with the fistula can be blocked with a bronchial blocker. The remaining lung can be mechanically
ventilated, and in the blocked part lung, a low level of continuous positive airway pressure can be applied to
prevent a full collapse without exacerbating a fistula
Obviously, the use of DLV in the ICU for a prolonged time can be associated
with several problems (such as possible tube disposition, obligatory muscle
relaxation, etc.). Therefore, the use of DLV in postthoracotomy patients is still
limited to patients, in whom mechanical ventilation is necessary, but the air leak
persists.
11.11 Weaning
An essential rule of mechanical ventilation is (or should be) that the weaning
should start – at least in the mind of the physician – when the mechanical
ventilation starts. Weaning from mechanical ventilation should be performed as
quickly as possible but not so fast as to be unsuccessful. Some criteria should be
fulfilled to obtain an uncomplicated extubation, no matter how long was the
duration of mechanical ventilation:
Normothermia
Cooperation
Sufficient coughing
Reliable spontaneous breathing and acceptable levels of pH, PaCO2, and
PaO2
One of the key points of a successful weaning is to follow a well-defined
protocol [35]. The weaning protocols should clearly define patients in whom
weaning should be tried, the methods and strategies of weaning, and what is
successful weaning (Fig. 11.5).
Fig. 11.5 Weaning protocol. A weaning protocol for patients with delayed tracheal extubation following
surgery including thoracotomy, which is used in the Istanbul Medical Faculty. Note that protocols can differ
between centers, but an institutional protocol should exist and be followed
Some rules for the successful weaning include:

Daily trials of spontaneous breathing: should be performed in every patient
who is mechanically ventilated more than 24 h to prevent remaining
“unrecognized”
Search and treatment of the reason of a failing trial
An algorithmic protocol that directs from controlled to supported
ventilation and from invasive ventilation to NIV
Prevention of oversedation (and also undersedation)
11.12 Tracheostomy
In cases of prolonged mechanical ventilation, or even a prediction of prolonged
mechanical ventilation of more than 7 days along with unsuccessful weaning
trials, tracheostomy should be considered. Even removing the tube and
associated tapes obtains reduced doses of sedatives. Moreover, and more
importantly, it eases mobilization and facilitates removal of tracheal secretions.
The patient may be able to eat, drink, and even speak. In spite of some contrary
studies, it is generally considered that early tracheostomy is associated with
easier weaning and a decrease in infections.
For postthoracotomy patients, surgeons tend to perform a surgical
tracheotomy, but as a routine practice of ICU, percutaneous tracheostomy is
easier, safer, and cheaper, at least in uncomplicated cases.
11.13 Management of Chest Tubes

For thoracic surgery, chest tube placement is a routine and almost mandatory
procedure. Therefore, the physician responsible for the postoperative care should
also be familiar with the management of the drainage of the thorax including
diagnosis and treatment of its complications. Chest tubes allow drainage of air
(ventral or cranial placement) and/or fluid (dorsal or caudal placement).
Therefore, the physician’s goal is to monitor, prevent, or treat air leaks and
excessive pleural drainage [36]. Via the classical three-bottle chest tube drainage
system (Fig. 11.6), the air from the pleura can be aspirated passively with a
water seal or actively by attaching a piped source of vacuum. There are
controversial reports regarding the effects of passive and active (or alternating)
suction [37, 38]. A balanced chest drainage system may be the most rational
strategy to maintain the mediastinum in a neutral position. If active aspiration is
chosen, the negative pressure should not exceed 15–20 cm H2O. Negative
pressure should be avoided after pneumonectomy, because it can cause
mediastinal shift. Tubes should never be clamped, for example, during patient
transport, because of the risk of tension pneumothorax.
Fig. 11.6 Three-bottle chest drainage system. Using the first (drainage collection) bottle only would cause
an increased resistance to drainage as a result of rising fluid/blood level and/or the foamy mixture of blood
and air in the bottle. Adding a second bottle (water seal) allows fluid to drain into the first bottle only and
the air into the second, also preventing the foam from forming. However, the added length of the tubing can
increase the dead space and add further resistance, causing a reversal of flow back up into the tube and back
into the pleural space. Therefore, a third bottle (suction control) allows for active suction to be exerted on
the system, preventing the chest tube effluent from going back toward the patient (Adapted from [40] (with
permission))
The volume of blood draining from chest tubes should be monitored,

especially during the early phase after the operation. Excessive blood drainage
should signal an emergency alarm to recall the surgeons. In later phases, chest
tubes are commonly left in situ when drainage was more than 250 ml per day.
However, this unproven measure was refuted in a recent study which found that
the chest tubes may be removed if the drainage is less than 450 ml per day as
long as there is no air leak, and the drainage fluid does not contain cerebrospinal
fluid, chyle, or blood [39]. Chest X-ray and chest tube status should be evaluated
simultaneously, and any discrepancy between them may indicate failing thorax
drainage because of tube blockage from kinking or clot or suction failure.
Conclusion
Today, only a few of the patients after thoracic surgery require – prolonged –
mechanical ventilation in ICU settings. However, it should be always kept in
mind that the postoperative mechanical ventilation can lead to additional
complications. In these cases, problems of other systems, such as cardiac
arrhythmias, fluid overload, etc., can worsen the conditions of the patient.
Mechanical ventilation should be considered only if necessary, but if necessary,
then as early as possible. During the mechanical ventilation, the recently
traumatized lung tissue should be protected; an aggravation of air leaks and
fistula should be prevented, with a least compromise of gas exchange. Weaning
should be considered as early as possible.
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DOI 10.1007/978-3-319-19908-5_12
12. Pros and Cons of Non-invasive

Ventilation After Thoracic Surgery
Lorenzo Ball1, Maddalena Dameri1 and Paolo Pelosi1
(1) IRCCS AOU San Martino-IST, Department of Surgical Sciences and
Integrated Diagnostics, University of Genoa, Genoa, Italy

Paolo Pelosi
Email: ppelosi@hotmail.com
12.1 Introduction
Thoracic surgical procedures have a significant impact on respiratory function,
mediated by multiple surgery-related and patient-related factors [1]. Thus,
thoracic surgery is at high risk for developing postoperative pulmonary
complications (PPCs), and attributable mortality due to postoperative lung injury
is higher compared to abdominal surgery [2]. Concerning patient-related factors,
most of the patients undergoing lung resection procedures have a history of
smoking and chronic obstructive pulmonary disease (COPD), contributing to this
increased postoperative risk [1]. Among procedure-related factors, general
anaesthesia, chest pain, phrenic nerve irritation, obliteration of distal airways and
loss of aerated parenchyma play a major role in determining postoperative lung
function impairment [3]. The lung and chest wall modifications that follow
thoracic surgery may determine the onset of hypoxemia, atelectasis and
pneumonia, potentially leading to acute respiratory failure (ARF) [4]. Thoracic
surgery has also been included as a specific risk factor in predictive scores aimed
at identifying patients at high risk of development of PPCs [5].
Non-invasive positive pressure ventilation (NPPV) can relieve dyspnoea and
improve respiratory function in the postoperative patient and has been proposed
for both preventing [6] and treating respiratory failure following thoracic
surgery. The aim of this chapter is to briefly describe the most commonly used
methods for delivering NPPV and their applications in the postoperative care of
the patient undergoing thoracic surgical procedures.
12.2 Non-invasive Positive Pressure Ventilation

Non-invasive ventilation (NIV) is a technique of ventilator support consisting in
the provision of mechanical ventilation without the need of an invasive artificial
airway [7]. Among the various non-invasive approaches, NPPV (non-invasive
positive pressure ventilation) delivered using different interfaces has become the
predominant technique, because of its effectiveness and convenience. Initially
used only for long-term assistance of patients with chronic diseases, NPPV is
being used increasingly in the last decades in selected cases of ARF, where it has
shown several advantages compared to intubation.
In fact, invasive mechanical ventilation is highly effective in supporting
alveolar ventilation, but endotracheal intubation carries several risks which can
be related to intubation and extubation manoeuvres, mechanical ventilation itself
and loss of airway defence mechanisms. NPPV can avoid many of these
complications because, since the upper airways are preserved, it reduces the
incidence of respiratory infections [8] and allows patients to expectorate
secretions spontaneously, verbalize and with some interfaces even drink and eat.
Despite the advantages of NIV, the lack of a direct connection to lower airways
poses several issues. The main absolute contraindications to NIV administration
are expectoration inability and airway obstruction at any level.
NPPV can improve the respiratory function in several ways. The main
mechanism of action through which NPPV relieves dyspnoea and restores
respiratory function is mediated by the reduction of the work of breathing [9].
This reduction in the work of breathing is the result of the intermittent
application of a positive pressure to the airways, increasing lung inflation and
tidal volumes while unloading inspiratory muscles. In the patient, this reduction
of energy consumption to maintain an adequate ventilation translates in a
reduced respiratory rate, use of accessory inspiratory muscles, dyspnoea and
CO2 retention in the alveoli [10]. NPPV can also guarantee an enhancement of
ventilation-perfusion ratio and a reduction of pulmonary shunt by increasing
functional residual capacity and thereby opening collapsed alveoli. Among the
other beneficial effects, NPPV produces an increase in intrathoracic pressure
which allows reducing both preload and afterload. The afterload reduction,
which is the greatest haemodynamic effect especially in patients with dilated
cardiomyopathy, leads to a trans-myocardial pressure reduction, thereby
potentially enhancing myocardial output. Several studies were focused on the
use of NIPPV to treat acute cardiogenic pulmonary oedema: patients treated with
non-invasive ventilation have shown a lower intubation rate and a more rapid
improvement of blood oxygenation [11].
NIV is most commonly employed to treat patients with chronic respiratory
failure: in these patients, long-term NIPPV is often administered night time
during sleep, in order to obtain a greater daytime gas exchange. The beneficial
effect of NIV on the respiratory function of these patients can be mainly
explained by an improvement of respiratory muscle function. NIV
administration during sleep allows fatigued respiratory muscles to rest,
improving daytime respiratory function [12], reducing respiratory work [13] and
modifying the respiratory centre set point for CO2 [12].
More recently NPPV has been introduced also for acute care application,
including the postoperative period. Several studies have been conducted to
compare traditional techniques and NPPV in critically ill patient’s management.
The greater advantage of this technique is the possibility to assist ventilation
without the need to invade the airways, which reduces the incidence of
infections. First of all, NPPV has been used to treat patients with acute
exacerbation of COPD. The most important registered effects are a reduction of
respiratory rate, a quick decrease of PaCO2 and a significant reduction of
intubation rate compared to standard care [7]. Another possible application for
NPPV is represented by the treatment of respiratory failure related to severe
pneumonia; patients treated with non-invasive ventilation have shown a lower
intubation rate [14], a shorter ICU length of stay and a significantly better short-
term survival. The use of NPPV as treatment for ARDS is considered
controversial. A recent multicenter randomized trial showed that, when used at
an early stage in mild ARDS, NPPV can reduce the intubation rate compared to
standard oxygen therapy [15]. Caution in this field is mandatory: patients should
be carefully selected in order to discriminate cases in which NPPV can be a
treatment option, from those where NPPV only represents a delay to a necessary
and unavoidable intubation.
12.2.1 NPPV in the Perioperative Period

Concerning the postoperative period, the interest towards NPPV is increasing in
the last decades. Several studies suggested a role for NPPV in treating
postoperative respiratory failure. Among others, a randomized, controlled,
unblinded study held on 209 patients that developed severe hypoxemia after
elective major abdominal surgery found that NPPV, compared to oxygen therapy,
reduced intubation rate and occurrence of postoperative pneumonia and sepsis
[16]. Nasal continuous positive airway pressure was proposed in a cohort of 56
patients undergoing elective prosthetic replacement of the thoracoabdominal
aorta, as a prophylactic measure to reduce the incidence of postoperative
respiratory failure: this approach leads to a reduction of incidence of PPCs, as
well as a reduction of hospital length of stay [17]. Most of the studies agree in
supporting the rationale of the use of NPPV as both a preventive and therapeutic
measure for postoperative pulmonary complications and respiratory failure,
especially in high-risk surgery.
12.2.2 Modes of NPPV

Virtually, any ventilation mode can be delivered through a non-invasive interface
instead of a conventional artificial airway [18]. Nonetheless, NPPV cannot be
simply considered interchangeable with conventional mechanical ventilation, for
the intrinsic non-hermetic nature of the system, resulting in a variable degree of
unavoidable air leaks, and for the variable resistance opposed by the upper
respiratory tract. In this paragraph the authors will briefly describe only the
ventilation modes that play a role in the postoperative period.
NPPV can be delivered with dedicated ventilators or with conventional ICU
ventilators. The formers are usually smaller and simpler to set up than the latters,
also because they are often designed also for home use in chronic patients. Their
ease of use might raise interest in the perioperative period, for the possibility of
initiating NPPV in the surgical ward where ICU ventilators are not promptly
available. These small ventilators can have a two-limb respiratory circuit, similar
to that of an ICU ventilator with a true expiratory valve allowing CO2 washout
or a single-limb circuit that permits exhalation and carbon dioxide removal
through a calibrated leak port [18].
12.2.2.1 Continuous Positive Airway Pressure

Continuous positive airway pressure (CPAP) is the provision of a constant
pressure to the non-invasive interface. It can be considered the simpler NPPV
mode, and it can be delivered with a ventilator or with high-flow systems,
consisting in a gas blender delivering a high flow to the patient, with the
pressure being set by means of a calibrated or adjustable PEEP valve. The
benefits of CPAP have been described initially in the treatment of acute
cardiogenic pulmonary oedema, subsequently in ARF, including in the
postoperative period. In CPAP, the patient fully controls respiration, deciding
frequency and duration of the respiratory cycle. Few studies investigated this
NPPV mode in patients that underwent lung resection [19].
12.2.2.2 Pressure Support Ventilation and Related

Ventilation Modes
Several modern dedicated ventilators and all ICU ventilators offer pressure
support ventilation (PSV) as an option. In this ventilation mode, the patient
controls directly the beginning of inspiration and indirectly the cycling into the
expiratory phase. Inspiratory trigger can be a fixed negative flow, typically
between −2 and −5 L/m, and, in ICU ventilators and several dedicated NPPV
ventilators, can be adjusted manually by the operator. Another common
inspiratory trigger is based on the detection of a decrease of pressure. Some
sophisticated ventilators especially designed for NPPV administration offer
algorithm-based flow-time curve analysis software that helps the ventilator to
distinguish genuine inspiratory efforts from artefacts due to air leaks.
Once the breath is triggered by the patient, the ventilator maintains a
constant desired pressure level. This pressure level can be maintained for a
preset duration (time-cycled ventilation) or until inspiratory flow decelerates
until a specific value (flow-cycled ventilation). In some home NPPV ventilator,
this flow value is fixed, but in most of the ventilators intended for in-hospital
use, this threshold can be set as an adjustable percent of the inspiratory peak
flow. In case of relevant air leaks, the flow delivered by the ventilator might
never reach this threshold value, leading to patient asynchrony. A recent
benchtop study showed that many ICU ventilators are not suitable for delivering
NPPV in case of large air leaks [20].
This ventilation mode is referred to with different names depending on the
ventilator manufacturer. PSV is the mode that was most extensively investigated
in the postoperative period after thoracic surgery.
12.2.2.3 Other Ventilation Modes

In some ICU ventilators, several ventilation modes are available that cycle
between two levels of constant pressure, allowing spontaneous unassisted
breaths at any pressure level. In most cases these ventilation modes are not
specifically designed for delivery through non-invasive interfaces; therefore, the
lack of air leak compensation can lead to an undesired loss of pressurization
[20].
Recently, humidified high-flow nasal cannulas (HHFNC) are under extensive
investigation for patients in ARF, also in the perioperative period. Their
mechanism of action is unclear and seems mediated by a flow-dependent CPAP
effect. Their role after thoracic surgery is still to be determined [21].
12.2.2.4 Interfaces
NPPV can be delivered through several types of interfaces: nasal masks,
oronasal masks, full-face masks and helmets [7]. Air leaks are a common
problem in the administration of NPPV; therefore, choosing the right interface,
tailoring it on the patient’s needs, is one of the most important aspects of a good
non-invasive respiratory support [22]. Choosing the optimal device allows to
reduce complications and discomfort, thereby optimizing patient compliance and
beneficial effects of the therapy [23].
Several models of interface are available on the market. Nasal interfaces
include nasal mask and nasal pillows: the former is a plastic mask with a soft
silicone pad which covers the nose, while the latter are soft rubber caps inserted
directly into the nostrils. Oronasal masks can be classified in facial masks,
covering the nose and mouth, and full-face masks, covering also the eyes.
Helmets are transparent PVC cylinder which includes the neck avoiding contact
with the face skin; these devices are usually equipped with anti-suffocation
valves, and the adhesion to the neck is guaranteed by an elastic collar attached to
padded straps. Each of these devices has advantages and disadvantages. A
simpler interface, the mouthpiece, allows to avoid several problems related to
the use of nasal or oronasal masks like skin lesion or claustrophobia [24], but the
need to a high level of patient cooperativeness [22] limits the interest of this
interface in the postoperative period. Nasal masks are usually well tolerated.
These devices allow the patient to eat, drink, expectorate and verbalize.
Compared to other interfaces, nasal masks have a lower dead space and tend to
cause less frequently claustrophobia, but they need a greater collaboration from
the patient and can cause skin breakdown as well as conjunctivitis or ocular
lesions due to the air leaks. Nasal pillows reduce decubitus and risk of skin
ulcers, but they are often associated with nasal irritation and lower seal at high
pressure [22].
Facial masks have a greater stability if compared with nasal masks and allow
a clearer monitoring of the air leaks. Because of their size, covering a larger part
of the face, they can cause claustrophobia, emesis and pressure sore, therefore
reducing patient compliance. Full-face masks are usually well tolerated because
they adhere on the perimeter of the face where the sensibility is lower. The size
of this device is larger than the others; they tend to reduce air leaks, therefore
determining a lower incidence of conjunctivitis. On the other hand, when the
mask is blurred the patient has a reduced visibility. Furthermore, a recent study
found out that these devices may be difficult to adapt to ICU ventilators [20].
The helmet is one of the most recently introduced interfaces. This device
completely eliminates the contact with the patient’s face and minimizes the risk
of skin breakdowns; therefore, the helmet can ensure greater comfort to the
patient also for prolonged NPPV administration [25, 26]. Conversely, this
interface presents several problems like excessive overall dimensions,
positioning difficulties and necessity of ventilators capable of delivering a high
airflow. The helmet hampers communication and increases respiratory dead
space. Moreover, helmets are not available in several countries where healthcare
authorities expressed concerns regarding the risk of CO2 rebreather through
these high-volume devices. In a randomized trial in patients developing
hypoxemic respiratory failure after surgery for aortic dissection, helmets were
found to be more rapid in improving gas exchange and better tolerated compared
to facial masks [27]. Similar results were found in a small matched-control study
in patients developing ARF after major abdominal surgery [28], while another
study showed slower PaCO2 decrease in COPD exacerbations treated with
helmets as compared to full-face masks [29].
Larger randomized trials are warranted to identify advantages of a specific
interface over the others, but the intrinsic necessity to tailor the interface on the
patient’s comfort should also be considered.
12.2.2.5 Humidification
When breathing in normal condition, the air is heated and humidified as it goes
through the airways. This obviously does not happen when the airflow is
generated by a machine, which produces cold and dry air. That’s why, although it
is often overlooked, humidification assumes an important role in NPPV.
Compared to invasive ventilation, NPPV respects the anatomy of the airways
and allows ventilation through natural ways.
Especially in case of a prolonged administration, the absence of
humidification can lead to several complications such as sore throat, reactive
cough, dry mouth, runny nose, nosebleeds, hoarseness and nasal congestion [30].
Although apparently trivial, these complications can be considered a leading
cause of reduced patient compliance, even in short-term administration, like the
case of postoperative NPPV. All these issues can be effectively reduced by
adding a humidification device to the circuit of NPPV [31].
We can distinguish two main categories of humidifiers: heated humidifiers
(HHs) and heat and moisture exchangers (HMEs). The formers are constituted
by a heating plate warming a water jar, to which the respiratory circuit is
connected. An adjustable thermostat allows the operator to set the temperature of
the water contained in the bell. The HME, frequently improperly referred to as
“filters”, can be distinguished in hygroscopic and hydrophobic filters. The
hydrophobic filters contain a ceramic fibre membrane that acts as a filter for
viruses and bacteria but allows only partial humidification. Therefore,
hydrophobic filters are generally placed at the proximal end of the circuit with
the main purpose of protecting the patient from contamination. The hygroscopic
filters are formed by a membrane filter of propylene with condensation surface,
usually made of paper and soaked with hygroscopic salts which guarantee
humidification. The newer HME filters combine the two types of membrane,
thus allowing both humidification and bacterial filtration. HHs are active
humidifiers, while HMEs are passive systems, only maintaining humidification
by retaining water vapour exhaled by the patient. The choice between HH and
HME filters requires a specific case-by-case trade-off analysis. HME filters are
easier to use and generally have a lower unitary cost. Among their main
limitations, it must be mentioned the increase of dead space during NPPV, which
results in an increased breathing effort and higher PaCO2 level when compared
to the HH systems [32]. On the other hand, HH filters are more expensive and
difficult to use, the circuit is prone to contamination and the optimal temperature
can be tricky to reach. In a randomized multicentre study, no differences were
observed between HH and HME in terms of reduction of the intubation rate [33].
When CPAP is generated with high-flow systems, HHs have been suggested to
be preferable [34].
12.2.3 NPPV After Thoracic Surgery

After lung resection surgery, lung function is more impaired compared to other
types of surgery because of the loss of parenchyma, thoracic pain, depression of
the respiratory drive due to high-dose systemic or epidural opiate use in the
perioperative period as well as closure of distal airways [7, 35]. There is an
increasing interest towards potential applications of NPPV after thoracic surgery,
and several small-sampled studies investigated its use both as a preventive and
curative measure in the postoperative period [4]. NPPV can be considered a
preventive measure when used routinely after lung resectional surgery,
especially in high-risk patients, to reduce the incidence of postoperative ARF,
aimed at reducing morbidity, the need of invasive mechanical ventilation and
finally mortality. Conversely, NPPV can be used as a curative intervention when
ARF is already established [36]. Even fewer studies investigated the possibility
of using NPPV as a preventive measure in the preoperative period [37].
Several authors suggested that, for the complexity of the management of
respiratory function after lung resection surgery, often it is not easy to
discriminate cases in which NPPV is used with a preventive intent from those in
which it is used as a therapeutic measure. In fact, in most cases it is applied in a
grey zone in which the aim is both to relief respiratory distress and improve the
clinical course of the patient, potentially reversing the pathway towards
respiratory failure [4, 6, 36].
12.2.3.1 Pathophysiology of NPPV After Thoracic

Surgery
The two most common major procedures in thoracic surgery are oesophageal
and lung resection interventions. Both procedures were for a long time
considered absolute contraindications for NPPV, for concerns regarding risks for
surgical anastomotic leak and for aspiration towards the airways [7]. Recently
several authors tried to challenge this assumption, based on pathophysiological
considerations, experimental models and clinical trials.
Concerning oesophagectomy, a recent study by Raman and colleagues [38]
investigated in a porcine in vivo and ex vivo model the air pressure tolerance of
an oesophageal anastomosis. Interestingly, the authors found an in vivo tolerance
without air leaks to pressures of 84 ± 38 cmH2O, much higher than the pressures
actually transmitted to the oesophagus during positive pressure ventilation. In a
retrospective clinical study on NPPV after oesophagectomy for oesophageal
cancer [39], the authors found that NPPV used as a first-line treatment for
postoperative ARF, by improving gas exchange, avoided intubation in nearly
half of the patients. The authors then concluded that NPPV may be an effective
option for ARF following oesophageal surgery.
The use of NPPV after lung resection surgery is mistrusted by surgeons and
often also by anaesthesiologists and intensive care physicians, for the concerns
that positive pressure ventilation could stress the bronchial suture or
anastomosis, increasing airway to pleural space leaks or, even worse, causing
anastomotic rupture. With a careful titration of NPPV, these concerns are
essentially unfounded and based on an erroneous interpretation of the
mechanisms leading to the anastomotic leakage. Indeed, the mechanical stress to
which the bronchial suture or anastomosis is subject is not proportional to the
airway pressure but rather to the difference between the inner airway pressure
(Paw) and the pressure of the space surrounding the anastomosis (Ppl). This
trans-anastomotic pressure gradient is responsible for the mechanical stress to
which airways are subject and corresponds to the transpulmonary pressure (PL =
Paw-Ppl) [40]. After thoracic surgery, a negative pressure is often applied to
chest tubes to promote lung expansion and to compensate parenchymal air leaks.
Since this negative pressure might contribute to an increase in transpulmonary
pressure, in some studies the temporary suspension of chest tube negative
pressure during NPPV administration was proposed as a precautionary measure
[19].
In the example shown in Fig. 12.1, NPPV is applied to a dyspnoeic patient in
ARF after lung resection surgery. As shown in the left panel, despite the small
swings in airway pressure, in spontaneous breathing the huge excursion in
negative pleural pressure, due to increased inspiratory effort, leads to a relevant
transpulmonary pressure. The application of an NPPV with low PEEP results in
an increase in airway pressure, but relieving inspiratory muscles allows a
reduction in pleural pressures. The resulting transpulmonary pressure during
NPPV has comparable average values and reduced peak.
Fig. 12.1 Pathophysiology of respiratory mechanics in a thoracic postoperative patient. The figures
illustrate airway (blue) and oesophageal (pink) pressure-time curves of a patient in respiratory distress in
spontaneous breathing (left) and during NPPV (right). Transpulmonary pressure (PL), also representing the
trans-anastomotic pressure gradient, is plotted in green. The vertical dashed line represents the beginning of
the expiratory phase
In a clinical study in 1997, Aguiló et al. [35] investigated the effects of short-
term (1 h) NPPV after lung resection surgery in ten subjects, compared to nine
controls. The author chose a BiPAP ventilation mode with an inspiratory
pressure of 10 cmH2O and an expiratory pressure of 5 cmH2O, delivered through
a nasal interface. The study concluded that short-term NPPV significantly
improved gas exchange without increasing either dead space or pleural air leaks
detected from the chest tube. Following this pivotal study, several small- to
middle-sampled studies investigated the efficacy of NPPV after thoracic surgery.
12.2.3.2 Evidence on Preventive Use of NPPV

Several studies investigated the role of NPPV as a preventive measure, namely,
routinely administered to all patients after thoracic surgery, in order to decrease
the incidence of respiratory events and to improve clinical outcome. Table 12.1
resumes the findings of the most relevant studies.
Table 12.1 Studies investigating the role of preventive NPPV after thoracic surgery
Author Year Type of Study design Patients NPPV in the Interface Main results
surgery intervention
group
Aguiló 1997 Pulmonary Physiological n = 20 PS = 10 Nasal Feasibility
[35] feasibility study Two cmH 2O Improved gas
groups PEEP = 5 exchange
cmH2O
Kindgen- 2005 Thoraco- Prospective RCT n = 50 CPAP = 10 Nasal Improved gas
Miles [17] abdominal Two cmH2O exchange
groups Reduced LOS
Perrin [37] 2007 Pulmonary Prospective RCT n = 34 PS = 10 Nasal Improved gas
(NPPV before and Two cmH2O exchange
after surgery) groups PEEP = 5 Reduced LOS
cmH2O
Liao [41] 2010 Thoracic Prospective RCT n = 50 IPAP = 13 ± Nasal or Improved lung re-
Two 3.2 cmH2O facial expansion at CT
groups EPAP = 4
cmH2O
Barbagallo 2012 Pulmonary Prospective RCT n = 50 High-flow Helmet Transient
[19] Two CPAP = 8 improvement in
groups cmH2O gas exchange
Lorut [42] 2014 Pulmonary Prospective RCT n = 360 PS = 10 Facial No significant
Two cmH2O difference in acute
groups PEEP = 5 respiratory events
cmH2O
RCT randomized controlled trial, PS pressure support, CPAP continuous positive

airway pressure, PEEP positive end-expiratory pressure, IPAP inspiratory
positive airway pressure, EPAP expiratory positive airway pressure
Several small randomized trials found an improvement in gas exchange [17,

19, 35, 37], and two of them also observed a reduction in hospital length of stay
[17, 37]. A single study investigated NPPV also preoperatively [37]. In a
randomized trial on 50 patients [41], NPPV improved lung re-expansion,
assessed by computed tomography, but no clinical advantage was found; in
particular the incidence of PPCs was not lower compared to the control group. In
a study using helmets for CPAP delivery [19], the advantages in gas exchange
improvement were found to be transient, rapidly returning to the baseline values
after the interruption of the CPAP administration.
In the largest randomized trial [42] in 360 COPD patients undergoing major
lung resection surgery, NPPV did not reduce the incidence of acute respiratory
events nor affected any of the secondary clinical endpoints, including ICU length
of stay, intubation rate and mortality. Even if a single middle-sized randomized
trial should not be considered definitive, these data suggest that administration of
preventive NPPV should not be considered as a standard approach for all
patients undergoing lung resectional surgery. It is difficult to aggregate the
results from other small studies, due to the heterogeneity of NPPV modes used,
interfaces and clinical outcomes. Further studies are necessary to identify
subgroups of patients at high risk that could potentially benefit from preventive
NPPV.
12.2.3.3 Evidence on Therapeutic Use of NPPV

Several studies investigated the role of NPPV as a therapeutic measure, namely,
administered to treat patients which developed ARF postoperatively. Table 12.1
resumes the findings of the most relevant studies. In a pilot study on 20 patients
meeting criteria for re-intubation after abdominal and thoracic surgery, nasal
CPAP was used as a method to avoid invasive ventilation [43]. In lung transplant
recipients, NPPV through face mask avoided intubation in most of the patients
that developed ARF postoperatively [44]. NPPV decreased mortality compared
to standard oxygen therapy in a randomized trial involving 24 patients in ARF
after lung resection [45]. The feasibility of NPPV in ARF following thoracic
surgery was further assessed in two prospective observational trials on a larger
cohort of patients [46, 47] (Table 12.2).
Table 12.2 Studies investigating the role of curative NPPV for ARF following thoracic surgery
Author Year Type of surgery Study design Patients NPPV Interface Main
mode results
Kindgen- 2000 Thoracic and abdominal Prospective, n = 20 CPAP = Nasal Improved
Miles [43] observational 10 gas
cmH2O exchange
Rocco [44] 2001 Pulmonary transplant Prospective, n = 21 PS = 14 Facial Feasibility
observational cmH2O Improved
PEEP = 5 gas
cmH2O exchange
Auriant 2001 Pulmonary Prospective n = 48 PS = 9 Nasal Intubation

[45] RCT cmH2O rate
PEEP = 4 decrease
cmH2O Mortality
decrease
Lefebvre 2009 Pulmonary Prospective, n = 113 PS = 14 Facial Feasibility
[46] observational cmH2O Success
PEEP = 5 rate of
cmH2O NPPV 85
%
Riviere 2010 Pulmonary or pulmonary Prospective, n = 135 PS = 14 Facial Feasibility
[47] thromboendarterectomy observational cmH2O Success
PEEP = 5 rate of
cmH2O NPPV 70
%
RCT randomized controlled trial, PS pressure support, CPAP continuous positive

airway pressure, PEEP positive end-expiratory pressure
12.3 Potential Limitations and Pitfalls of NPPV

NPPV should be administered in the right cases in the right time window.
Indeed, NPPV should be considered a measure to support the respiratory
function while the underlying reversible condition is treated. Further studies are
warranted to help the clinician in individuating thresholds and clinical scores to
identify patients that can benefit from preventive or curative NPPV.
It is a matter of debate whether postoperative NPPV for ARF should be
administered only in the ICU setting [48]. As a general principle, administration
of NPPV should be accompanied by adequate respiratory monitoring [49]. In
many hospitals ventilators are not available in the medical ward, but this issue
could be circumvented by the use of small portable ventilators. In a feasibility
study of NPPV in the recovery room of the general surgery, the use of NIV-
dedicated small ventilators was proposed and found to be a viable option for
relieving ARF in the immediate postoperative period [50]. A recent study in the
United States [51] found that most NPPV treatments for ARF were initiated in
the ICU or in the emergency department and general wards. NPPV feasibility
and efficacy were found to be comparable in different age groups [52].
For the importance of adequately monitoring gas exchange and airway
pressures, the authors of this chapter recommend a cautious approach to this
very specialized application of NPPV, reserving its use in a clinical setting with
an adequate number of trained nurses and respiratory caregivers, with
continuous monitoring of SpO2, blood pressure, respiratory rate and airway
pressure. It has been recently shown that the delivery of NPPV by a dedicated
trained team can reduce intubation rate and risk of death during non-invasive
ventilation [53]. The availability of an intensivist 24 h per day within few
minutes from the patient is mandatory: in case of NPPV failure, a rapid
intubation and transfer to an ICU for invasive mechanical ventilation should not
be delayed.
Conclusions
In the postoperative period after thoracic surgery, NPPV can be a tool to support
respiratory function and to avoid unnecessary intubation, potentially reducing
morbidity and mortality. Its safety and feasibility have been validated in several
trials. There is not enough evidence to support the use of routine administration
of NPPV as a preventive measure in all patients undergoing thoracic surgery.
Concerning the therapeutic use in postoperative respiratory failure, there is
evidence supporting the feasibility, safety and efficacy of NPPV as a treatment
for ARF following thoracic surgery.
A compromise between a good gas exchange and an acceptable mechanical
stress to the anastomosis must be individuated: the authors suggest using a low
PEEP level (≤5 cmH2O) and the lowest possible pressure support level.
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DOI 10.1007/978-3-319-19908-5_13
13. Lung Surgery and Extracorporeal

Oxygenation
Edda M. Tschernko1 and Clemens Aigner2
(1) Department of Cardiothoracic Anesthesia and Intensive Care Medicine,
Vienna General Hospital, University of Vienna, Vienna, Austria
(2) Department of Thoracic Surgery, Vienna General Hospital, University of
Vienna, Vienna, Austria

Edda M. Tschernko
Email: edda.tschernko@meduniwien.ac.at
13.1 Introduction
Extracorporeal assist devices, such as extracorporeal membrane oxygenation
(ECMO) or heart-lung machine, have been used in selected centers before,
during, and after thoracic surgery. Especially the use of ECMO, before (even in
awake patients = awake ECMO) [1], during, and after lung transplantation is
well established in various centers. Additionally, extracorporeal devices are used
in selected patients undergoing extended lung surgery with necessary resection
of adjoining vessels or parts of the heart such as the atrium. For complicated
tracheobronchial surgery, an extracorporeal device can be of crucial help during
the surgical procedure and guarantee for patient safety.
Special considerations for lung transplantation will not be discussed in detail,
since it deals with special problems associated with transplant patients and organ
selection. In this chapter the use of extracorporeal support during complicated
lung surgery and tracheobronchial resection will be dealt with. Nevertheless,
lung transplantation will be addressed several times, because extracorporeal
devices are commonly used for lung transplant, whereas non-transplant lung
surgery with extracorporeal devices is still relatively rare. Advantages and
disadvantages as well as indications, complications, and outcome will be
critically focused on.
13.2 Technology
Various devices are commercially available. Technical considerations like
resistance of oxygenator membrane, maximal duration of use, filling volume,
and feasibility for transport can play a substantial role in the selection of a
specific device.
In general the main components (Fig. 13.1) of extracorporeal devices are an
oxygenator, a centrifugal pump, a tube set, and a device for flow measurement.
The system is nowadays completely heparin coated. Therefore, heparin has to be
administered in relatively low doses [2]. Usually a single shot of heparin 70
IE/kg body weight is administered before the start of the device. The target
activated clotting time (ACT) is 160–180 s (measured hourly during surgery).
Alternatively aPTT can be used to monitor anticoagulation (aim: aPTT 55–60s).
For prolonged use of an extracorporeal device, a heparin bypass is used to avoid
clotting of the blood. Advantages and disadvantages of various extracorporeal
devices are shown in Table 13.1.
Fig. 13.1 The main components of ECMO are displayed in Fig. 13.1. A venoarterial ECMO is shown in
Fig. 13.1. The cannulation site of ECMO is central, via the internal jugular vein and the carotid artery or via
the femoral vein and femoral artery. According to the site of cannulation specific complications can occur,
e.g., lymphatic fistula in the groin
Table 13.1 Comparison of extracorporeal assist devices

Gas exchange ↓ C LV ↓ High PAP Tracheobronchial res.
ILA CO2 removal − − − −
VV-ECMO CO2 + O2 − − − +
VA-ECMO CO2 + O2 + + + +
HLM CO2 + O2 + + + +
Alternative Ventilation (I/NI) Inotropes Inotropes Prostin/NO Jet ventilation
ILA interventional lung assist, VV-ECMO venovenous ECMO, VA-ECMO

venoarterial ECMO, HLM heart-lung machine, alternative alternative
therapeutic options, gas exchange ↓ impaired gas exchange, RV ↓ impaired right
ventricular function, LV ↓ impaired left ventricular function, high PAP high
pulmonary artery pressure, tracheobronchial res. tracheobronchial resection
13.2.1 Interventional Lung Assist
This arteriovenous device is driven by the cardiac pump function of the patient
because no centrifugal pump is included. Thus, the precondition for the use of
interventional lung assist (iLA) is a patient with uncompromised cardiac
function. Percutaneous cannulation of the tubes is usually performed via the
femoral artery and the femoral vein [3]. Central implantation via the pulmonary
artery and the left atrium has been described for bridging of patients with
pulmonary hypertension [4, 5]. The oxygenator has a low resistance and the
priming volume is no more than 200 mL. Only part of the cardiac output is
passing through the oxygenator membrane. Therefore, CO2 elimination can be
sufficiently provided by an oxygenator flow of no more than 500–1000 mL/min
[6]. Oxygenation would require a flow of at least 2000 mL/min. An
interventional assist device is shown in Fig. 13.2. The major advantage of this
device is the low priming volume. However, this device is mainly used for CO2
removal.
Fig. 13.2 Interventional assist device is displayed in Fig. 13.2
13.2.2 Venovenous ECMO

The precondition for the insertion of this device is a hemodynamically stable
patient with no relevant pulmonary hypertension. Venovenous ECMO can
guarantee for sufficient gas exchange (CO2 elimination and oxygenation) at flow
rates up to 4000 mL/min. Standard cannulation drains the blood via the right
femoral vein from the vena cava inferior and recirculates the blood via the right
jugular vein to the right atrium. Sufficient distance between the cannulas is
essential to avoid recirculation of the blood in the oxygenator.
13.2.3 Venoarterial ECMO

The venoarterial ECMO is a rather invasive form of extracorporeal device. The
blood is drained from the right atrium pumped through the oxygenator and
recirculated via a large systemic artery (Fig. 13.1). By means of this technique,
hemodynamic support is provided and the circulation through the lung is
substantially reduced. Cannulation can be performed via the right atrium and the
ascending aorta for exclusively intraoperative use and via the femoral vein
(drainage of blood from the right atrium) and the femoral artery (recirculation of
oxygenated blood) for prolonged postoperative use. The tip of the arterial
cannula is situated in the descending aorta. Thus, the cardiac output from the
heart (gas exchange through patient’s lung) and the recirculated blood from the
venoarterial ECMO mix in the descending aorta. This fact may lead to
substantially different oxygenation in the upper and lower part of the body.
Monitoring of oxygenation has to be performed on the right arm because it is
most likely to achieve similar values compared to the cerebral oxygenation.
13.2.4 Heart-Lung Machine

This extracorporeal support is exclusively used during surgery. The patient has
to be fully heparinized for the use of this device. Therefore, surgical bleeding is
a feared complication associated with the use of the heart-lung machine.
Additionally, it should not be used for oncological procedures because systemic
spread of tumor cells should be avoided in these patients.
13.3 Indications for the Use of an Extracorporeal Device

Before, During, and After Surgery
The indications for the use of an extracorporeal device in lung surgery are
displayed in Table 13.2. Basically the pre-, intra-, and postoperative use of an
extracorporeal device can be necessary due to pulmonary malfunction (impaired
gas exchange), cardiac malfunction (right and/or left ventricular failure), or a
mixture of both. The crucial question for all situations with the need for an
extracorporeal @device is will the situation improve after surgery? Or in other
words: Can medical and/or surgical treatment improve the underlying organ
malfunction to an extent that the patient can be successfully weaned from the
extracorporeal device after a reasonable time span?
Table 13.2 Advantages of various methods used during tracheobronchial resection
Cross table iLA ECMO HLM
Jet ventilation
Risk for bleeding + ± ± −
Hemodynamic stability − − + +
Gas exchange stability − ∓ + +
Surgical sight − + + +
13.3.1 Impaired Gas Exchange on the Basis of Lung

Disease
Several underlying pulmonary diseases result in impaired gas exchange with
potential respiratory decompensation. Chronic obstructive pulmonary disease
(COPD) is the most frequent indication for lung transplantation in most
institutions [6]. In these patients extracorporeal devices are frequently used
before, during, and after lung transplantation to guarantee for respiratory and
hemodynamic stability. Additionally, acute pulmonary infections in COPD
patients occur frequently and lead in some cases to fetal impairment in gas
exchange. This situation may occur while a patient is on the waiting list for lung
transplant. Especially in young patients an extracorporeal device can be used to
overcome the critical time of infection.
However, in this chapter the focus is on patients with severe COPD
presenting for non-transplant lung surgery. Malignancies of the lung may create
the need for a surgical procedure in these patients. The crucial question is: Does
it make sense to use extracorporeal devices during lung surgery because of
severe COPD? Only close cooperation of pulmonologists, lung surgeons,
anesthesiologists and intensivists can answer this question for the individual
patient. Lobectomy or even pneumonectomy can lead to substantial
improvement in gas exchange if the removed lung does not participate in
ventilation due to occluded bronchial parts. Or the removal of hyperinflated
areas (lung volume reduction surgery) may result in substantially improved
ventilator mechanics. The blood flow through the lung tissue not participating in
gas exchange is redistributed to well-ventilated areas, and thus, intrapulmonary
shunt reduced [7]. If the patient´s gas exchange is already severely impaired
before surgery extracorporal support can be necessary during a brief
intraoperative time span (e.g. during single lung ventilation). Which device
chosen will be dependent on considerations including the risk of bleeding,
hemodynamic stability, gas exchange and surgical sight (Table 13.1 and 13.2).
However, in most cases less invasive measures will be sufficient to overcome the
critical time span during surgery, e.g., permissive hypercapnia, FiO2 of 100 %,
jet ventilation, etc. The patient’s medical situation and local preferences of the
surgical team are usually crucial in the choice of gas exchange support.
13.3.2 Impaired Right Ventricular Function Due to

Pulmonary Hypertension
13.3.2.1 Chronic Thromboembolic Pulmonary
Hypertension
Impaired right ventricular function is regularly observed in patients with chronic
thromboembolic pulmonary disease due to high resistance in the pulmonary
circulation. Surgery for chronic thromboembolic pulmonary hypertension
(CTEPH) aims at the removal of embolic material in the pulmonary vessels, thus
leading to reduced resistance in the pulmonary circulation [8]. It is a well-
established procedure with reasonable success rates [7, 9]. This procedure is
usually undertaken while the patient is in hypothermic cardiopulmonary arrest.
Surgery for CTEPH requires therefore the use of a heart-lung machine (HLM).
At our institution about 30–40 cases are performed per year. Appropriate patient
selection and standardization of the intraoperative and postoperative care lead to
perioperative mortality rates of no more than 5 % [10]. For this very special
procedure the HLM is a precondition.
13.3.2.2 Primary Idiopathic Pulmonary Hypertension

(PIPH)
The reasons for the development of primary idiopathic pulmonary hypertension
(PIPH) are not known to date [11]. However, PIPH frequently develops in young
subjects. The medical therapy with prostaglandines, endothelin 1 receptor
antagonists or phosphodiesterase 5 inhibitors. can help to a certain extent. As
PIPH progresses, a remodeling of the heart occurs. The right ventricle increases
in dimension and forms the apex of the heart [12]. Usually a tricuspid
insufficiency is present and the septum bulges toward the left ventricle during
systolic action. The left ventricle decreases in dimension and its systolic and
diastolic function deteriorates [13]. This condition is an indication for lung
transplant surgery. During surgery an extracorporeal device (at our institution
venoarterial ECMO is used) is necessary for hemodynamic stability and to
guarantee for adequate gas exchange. Usually the extracorporeal device will be
required for several days after lung transplant to avoid volume overload of the
“untrained” left ventricle [14].
If surgery other than transplant becomes necessary in patients suffering from
severe PIPH, high attention has to be paid on adequate monitoring of the
pulmonary artery pressure and cardiac function. Therefore, a Swan-Ganz
catheter in combination with a transesophageal echo may be required for even
trivial surgery to avoid any risk of cardiac decompensation during general
anesthesia.
13.3.3 Tracheobronchial Surgery and Extended Lung

Surgery
For tracheobronchial resections required for the removal of malignancies or
benign tracheobronchial diseases, it is a challenge to combine adequate
ventilation and proper operative sight [15]. Standard procedures like resection of
a small part of the trachea are usually undertaken with cross table ventilation,
e.g., sterile ventilator tubing is used close to the operative field [16]. However,
this may lead to substantial difficulties for the surgeon to access the surgical
field (16). As an alternative, parts of the surgery can be undertaken during apnea
or jet ventilation. However, limitation of surgical time during apnea or potential
spread of tracheobronchial secretion and/or tumor cells during jet ventilation is
undesirable. To avoid this, the use of HLM has been well established for
tracheobronchial resections [17–18]. Hemodynamic stability and adequate gas
exchange in combination with proper sight on the operative field are guaranteed
if HLM is used during complicated tracheobronchial resection or reconstruction.
However, the need for anticoagulation may lead to increased frequency of
bleeding and transfusion [19]. To avoid the disadvantages of systemic
anticoagulation, iLA or ECMO with roller pump can be used. The advantages
and disadvantages of the most frequently used approaches are shown in Table
13.2.
13.4 Summary
Various extracorporeal devices are available to support gas exchange and
hemodynamic stability before, during, and after lung surgery. The use of these
devices changed from being a clinical experiment in a desperate situation to
routinely planned procedures for special patients and extended surgery. This
development was initiated clearly by the use of extracorporeal devices for lung
transplant surgery dealing with severely limited patients for a complicated
surgical procedure such as transplant. The improvement of technology of the
devices increases which leads to an improved risk/benefit ratio. For patient
safety during extended or small procedures in pulmonary and/or circulatory
severely limited patients, the use of extracorporeal support becomes more and
more common for clinical routine. However, it has to be kept in mind that all of
these devices are bridging tools. For surgical success the precondition is that the
patient’s situation can be substantially improved by surgery and medical therapy
within a reasonable time span. Close cooperation of surgeons, pulmonologists,
anesthesiologists, and intensivists is necessary for adequate indication of the use
of an extracorporeal device before, during, or after lung surgery or complicated
lung resection or tracheal resection. The choice of the device is dependent on
advantages and disadvantages associated with the device, the patient’s
morbidities and comorbidities and the experience of the institution. However, the
use of extracorporeal devices for lung resection or complicated tracheal resection
or reconstruction still has to be called “experimental.” Nevertheless, it can be a
suitable and lifesaving tool if indications are considered carefully and the
procedure is carried out by an experienced team of experts.
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DOI 10.1007/978-3-319-19908-5_14
14. Pneumonia After Thoracic Surgery

Perihan Ergin Özcan1 and Evren Şentürk1

Perihan Ergin Özcan
Email: pergin@istanbul.edu.tr
14.1 Introduction
The developments in the field of thoracic surgery and perioperative anesthetic
management have extended its patient population; those who were previously
inoperable are now undergoing surgery.
Preoperative evaluations by a multidisciplinary team that includes thoracic
surgeons, chest physicians, intensive care physicians, and anesthesiologists have
benefited patients in terms of reduced postoperative morbidity and mortality.
The causes of postoperative complications can be divided into three
categories: infectious, surgery related, and cardiovascular. The most frequent and
severe complications after thoracic surgery are respiratory complications. Some
are surgery related such as hemorrhage, bronchopleural fistula, and atelectasis.
Other respiratory complications are pneumonia, acute lung injury, and acute
respiratory distress syndrome (ARDS). Hypoventilation and ineffective cough
caused by several mechanisms such as inappropriate pain management increase
the risk of postoperative pneumonia. There are also cardiovascular complications
including arrhythmias, pulmonary thromboembolism, and cardiac failure.
The incidence of pneumonia after thoracic surgery is approximately 5.3–22
% [1, 2]. Factors that influence the incidence of pneumonia include patient
population, type of surgery, antibiotic prophylaxis, and diagnostic criteria for
pneumonia. The incidence of pneumonia is higher when using clinical criteria
compared with objective criteria.
The mortality rate of postoperative pneumonia is approximately 17 %; after
thoracic surgery the rate rises to 19–40 % [1, 3]. Due to the high risk for
mortality in this patient population, risk prediction is also crucial for surgical
decision-making and informed patient consent. Pneumonia after thoracic surgery
causes longer stays in intensive care units (ICU) and hospitals, which in turn
increases the costs.
14.2 Risk Factors

During the perioperative period, many risk factors play a role in the development
of postoperative pneumonia. With the exception of abdominal surgery, the risk of
pneumonia after thoracic surgery is 38 times greater than other type of surgery
[4]. Deterioration in pulmonary function after abdominal and thoracic surgery
has previously been evidenced through pulmonary function tests, imaging
methods, and physiologic measurements [5, 6].
The risk factors for postoperative pneumonia after thoracic surgery can be
separated into three phases as the preoperative, intraoperative, and postoperative
periods.
Risk factors related with postoperative pneumonia in thoracic surgery are
listed in Table 14.1 [7, 8].
Table 14.1 Risk factors for postoperative pneumonia after thoracic surgery
Age ≥ 75
Male
Smoking history
FEV1 < 70 %
Induction therapy
Pathologic stages III–IV
Duration of operation > 3 h
COPD
Histopathologic type (squamous cell carcinoma)
FEV 1 forced expiratory volume in one second, COPD chronic obstructive

pulmonary disease
Arozullah et al. used a combination of risk factors to create a risk index for
predicting pneumonia after noncardiac surgery [9]. The authors developed the
risk index from the data obtained from preoperative patient-specific and
operation-specific risk factors. They found that abdominal aortic aneurysm
repair and thoracic surgery had the highest risk for postoperative pneumonia.
The risk index may be useful for high-risk patients; therefore giving these patient
groups more attention in the perioperative period and taking preventive measures
may reduce the incidence of pneumonia.
Predictors of postoperative pneumonia are explained in some other chapters
of this book; there we are going to focus on approach during postoperative
period.
14.3 The Postoperative Period

Secretions cause atelectasis and pneumonia during the postoperative period,
especially in patients with a smoking history, pain, and inefficient cough.
Secretion retention in airways may cause obstruction of broncopulmonary units
and atelectasis, and this is even more pronounced in smokers and in patients with
chronic lung disease. The diagnosis of sputum retention can be clinical and it is
characterized by respiratory distress with rapid, shallow, and bubbly breaths.
There was a strong association between sputum retention and postoperative
pneumonia in patients with chronic obstructive pulmonary disease (COPD),
smoking history, and poor analgesia [10]. There is a great importance for
physiotherapy in this situation. At least two daily visits should be performed;
some patients need more. Another noteworthy point is the hydration of patients
for secretion mobilization. Oxygen therapy via a facemask inevitably dries
secretions when non-humidified oxygen is used. This causes mucociliary
dysfunction and a decreased ability to clear secretions, so humidified oxygen
should be used. Sometimes mucolytic agents can be helpful. Chest
physiotherapy is a therapeutic modality that should be kept in mind. Postural
drainage, percussion, and vibration are applied to the affected lung opening and
promote coughing during which physicians should provide adequate analgesia.
Despite these interventions, tracheal suctioning can be used in patients who
cannot remove secretions. Before suctioning, high oxygen fraction should be
used in patients at risk for hypoxemia.
Fiberoptic bronchoscopy may be used for clearance of secretions which has
the advantage of direct visualization of the tracheobronchial tree and the ability
to take sputum samples for culture when a clinically infection is suspected.
Sedation is required for this procedure in nonintubated patients; noninvasive
ventilation may be used during the intervention to avoid hypoxemia.
14.4 Pulmonary Rehabilitation
Many comorbid conditions accompany lung cancer surgery. Approximately 50
% of patients with lung cancer also have COPD [11]. Patients with COPD may
have ineffective cough, increased secretions, and impaired gas exchange after
lung resections, especially hypercapnia secondary to hypoventilation. Some
patients may need re-intubation and mechanical ventilation. Pulmonary
rehabilitation includes breathing exercise, cough training, and self-management
education; psychosocial support has been shown to decrease complications [12,
13]. Preoperative assessment of these patients for targeting reduces postoperative
complications and improves survival. Pneumonia is the most significant
postoperative complication that increases morbidity and mortality. These
interventions may help reduce the incidence, severity, and risks of pneumonia.
Smoking cessation and pharmacological therapies such as bronchodilators,
mucolytics, and antibiotics if necessary are useful for patients preparing for lung
resection and also those with chronic lung disease.
Pulmonary rehabilitation programs can be preoperatively and postoperatively
conducted at certain time periods. These programs include breathing and
coughing techniques, inspiratory muscle strength, home-based aerobic exercise,
and incentive spirometry [14–16]. Spruit et al. showed that patients with poor
functional status after lung cancer treatment improved their exercise capacity
using a pulmonary rehabilitation program with a 6-min walk [17]. However,
after patients are diagnosed as having lung cancer, they often feel that surgery
must be planned as soon as possible and thus may refuse a pulmonary
rehabilitation program.
14.5 Analgesia
The thoracic analgesia is crucial to keep the patient comfortable for reducing
postoperative pulmonary complications after surgery. Surgical incision,
intercostal nerve injury, and inflammation are major causes of pain after thoracic
surgery. Thoracic epidural analgesia is still considered the gold standard for pain
relief after thoracotomies, but recently some evidence showed that a
paravertebral block had a similar analgesic effect with fewer adverse effects than
thoracic epidural analgesia [18]. For reduced complications after thoracic
surgery, patients should be able to breathe deeply, cough, and remove secretions
and should be mobilized early. Postoperative ineffective pain relief associates
with worsened pulmonary complications. Belda reported that a higher
postoperative pain score was an independent predictor of postoperative
respiratory infections [19]. Recently, multimodal analgesia has been preferred
for post thoracotomy pain. In this regimen, regional blocks are combined with
opioids, nonsteroidal anti-inflammatory drugs, acetaminophen, selective
cyclooxygenase −2 inhibitors, and α2 agonists. Multimodal analgesia is more
effective and has fewer adverse effects. When the age and comorbid conditions
of these patients are considered, more attention must be paid to the drugs used
for analgesia in this population.
14.6 Does Bronchial Colonization-Airway Colonization

Play a Role in Postoperative Pneumonia After Thoracic
Surgery?
In normal conditions, the lower respiratory tract is sterile. Most patients who
undergo surgery have a history of smoking with subsequent impairment of
mucociliary function and accumulation of secretions in the lung; therefore these
patients have facilitating factors for the development of infection.
The source of pathogenic microorganisms responsible for pneumonia in this
patient population is not yet clear. Preoperative colonization, colonization during
intubation or mechanical ventilation, and aspiration during the perioperative
period can cause pneumonia after thoracic surgery [20]. The incidence of airway
colonization in patients with lung cancer varied between 10 and 83 % [1, 19,
21]. Taking samples using different methods (bronchoalveolar lavage (BAL),
protected specimen brush (PSB), endotracheal aspiration (ETA), spontaneous
sputum) and at different times (preoperative, perioperative, or postoperative
period) may account for this wide range.
Some studies have been shown that healthy, nonsmoking patients have no
airway colonization [22, 23]. Healthy smokers and patients with COPD had
bacterial colonization at 29 % and 66 %, respectively [24, 25]. Monso showed
that 25 % of 40 stable patients with COPD had airway colonization; the most
commonly isolated microorganisms were Haemophilus influenzae and
Streptococcus pneumonia [26].
Patients who undergo thoracic surgery have similar colonization patterns to
patients with COPD. Although the relationship between airway colonization and
ventilator-associated pneumonia has been proven, bronchial colonization and
pneumonia in patients after lung cancer surgery are unclear. Several studies
investigated this issue. Hirakata et al. investigated the airway colonization
patterns in patients with primary lung cancer and nonmalignant lung disease and
healthy volunteers [27]. The rate of bacterial colonization was significantly
higher in patients with lung cancer (51.9 %) than in those with nonmalignant
lung disease (37.3 %) and healthy volunteers (37.8 %), and the Gram-negative
colonization was higher in this cancer group than in other patient populations.
The pathogenesis of airway colonization in patients with lung cancer is not clear,
but centrally located tumors and high body mass index were found to be risk
factors for colonization [28]. Smoking and poor pulmonary functions also add
risk for colonization in patients with COPD. Furthermore, sampling methods that
evaluate the incidence of airway colonization are imperative in this patient
population.
Which time period is important to the development of pneumonia with
respect to colonization? Sok et al. performed a study to verify the origin of
microorganisms that caused pulmonary infections after lung cancer surgery [29].
They obtained samples of sputum 3 days before surgery, during surgery, and 3
days after surgery. The microorganisms that caused infections were isolated as
preoperative 18 %, intraoperative 13 %, and postoperative 63 %. They found
that the microorganisms which caused pneumonia were the same with
microorganisms which were isolated in sputum at the 3rd postoperative day. The
authors concluded that the colonization of the airway usually occurs during the
postoperative period; the oral cavity and pharynx were the source of pathogens.
Cabello et al. investigated distal airway colonization in patients with
pulmonary carcinoma and obtained samples from proximal to the endobronchial
lesion using a PSB [22]. They used ≥102 cfu/mL as a cutoff value for
colonization and found that 42 % of patients had bronchial colonization. Sixteen
of 25 isolated microorganisms were non-potential pathogenic microorganism,
and the most isolated potential pathogen microorganism was H. influenza.
Similarly, Ionas et al. found 41 % bronchial colonization in patients with
resectable lung cancer [28].
Rather than the colonization of the airway, the similarity of microorganisms
that colonize the airway and cause pneumonia is a more relevant issue. The
correlation between these pathogens is controversial. Ionas reported that there
was no relationship between postoperative infectious pulmonary complications
and bronchial colonization [28]. Sok demonstrated that postoperative infective
complications were caused by Gram-negative bacteria, whereas most of the
positive cultures obtained preoperatively were Gram positive [29]. The change
in the pattern suggests that the colonization of microorganisms in the early
postoperative period may be caused by the aspiration of gastric contents and
frequent interventions to the airway in the operating room and ICU. In contrast
to these studies, some authors reported a good correlation between
microorganisms isolated from patients who developed postoperative pneumonia
with the same agents identified preoperatively [1, 19, 21, 30]. Appropriate
prophylactic antibiotics and optimal duration of prophylaxis are the most
imperative considerations for the prevention of postoperative pneumonia in
patients who are colonized with potentially pathogenic microorganisms (PPMs)
preoperatively.
The most common preoperatively isolated microorganisms from the airway
are H. influenzae, S. pneumonia, and Staphylococcus aureus. Although
approximately 50 % of postoperative pulmonary pathogens are not documented,
some of the isolated pathogens have been different in various studies. In
pneumonia developed during late postoperative period, resistant strains of gram-
negative bacteria should be considered as potential pathogens. In the early
postoperative period (first week), H. influenzae and S. pneumonia are the most
common pathogens, but more resistant microorganisms such as Pseudomonas
aeruginosa, Acinetobacter baumannii, and Klebsiella pneumonia cause
pneumonia in the late postoperative period. Cytomegalovirus (CMV) infection in
patients with hematologic malignancies, patients who are human
immunodeficiency virus positive, and lung transplant recipients is common, but
the incidence of CMV infection in other types of cancer patients is not well
known. A study performed in a surgical ICU showed that the incidence of CMV
infections was around 35.6 % [31]. The essential thing here is to suspect a CMV
and make the correct diagnosis, especially in patients under treatment with
steroids. Preemptive antiviral therapy is administered in selected patient
populations but not in thoracic surgery. Antiviral therapy should be considered
for patients with severe pneumonia, ARDS, and resistant to classical
antibacterial therapy in postoperative period especially for patients who
underwent induction therapy. The widespread use of antibiotics also affects the
type of microorganisms that colonize.
14.7 Antibiotic Prophylaxis

Antibiotic prophylaxis should be used for thoracic surgery because of the clean
contaminated nature of these operations. The relationship between airway
colonization during the perioperative period and postoperative pneumonia after
thoracic surgery enhances the significance of antibiotic prophylaxis in this field.
Despite the routine use of antibiotic prophylaxis, the incidence of postoperative
pneumonia is also high (24 %) [1, 2]. In several studies the onset of
postoperative pneumonia developed in the first week.
Which type of prophylactic antibiotics is recommended in this type of
surgery? First- and second-generation cephalosporins such as cefazolin,
cefamandole, cefuroxime, and cefepime are the most frequently used agents for
prophylaxis in pulmonary resections in many countries. These agents are highly
successful in preventing surgical wound infections but their effectiveness in
pneumonia should be questioned [32]. In a study that investigated the efficacy of
prophylaxis, it was shown that the microorganisms that caused pneumonia were
not sensitive to prophylactic antibiotics [32].
Most of the microorganisms responsible for postoperative pneumonia are
Gram negative and are resistant to first- and second-generation cephalosporins.
Preoperative microbiologic examination of the tracheobronchial tree may be
helpful to select effective antibiotic prophylaxis. Several studies investigated the
effect of different prophylactic agents on postoperative pneumonia (1, 33).
Schussler compared cefamandole (3 g/24 h) with amoxicillin-clavulanate (6 g/24
h) and found a significant decrease in the incidence of postoperative pneumonia
in the second group and concluded that antibiotic prophylaxis may decrease the
rate of pneumonia after surgery. Another study compared cefuroxime and
cefepime and found that cefuroxime was more effective than cefepime as a
prophylactic agent [33]. Most of the microorganisms responsible for
postoperative pneumonia are Gram-negative bacteria, and 50 % of them are
Enterobacteriaceae spp., which are resistant to these antibiotics [32].
The dose and duration of antibiotics used for prophylaxis are another major
challenge. The first dose is usually administered after the induction of
anesthesia. Some protocols only use a single dose, whereas other protocols use
antibiotics for 24 or 48 h for prophylaxis [34].
Skin and oropharyngeal flora can be the source of microorganisms that cause
postoperative pneumonia after thoracic surgery. Therefore antibiotic prophylaxis
should be considered before surgery and in cases of pneumonia microorganisms
from the skin, and oropharyngeal flora must be covered.
Microorganisms that colonize the bronchial tree are usually responsible for
postoperative pneumonia. In addition to antibiotic prophylaxis, surveillance
results and antibiotic sensitivity patterns should be considered.
Using classical criteria for diagnosis of pneumonia after lung resection is
more difficult than other types of surgery because fever, hypoxemia, and
abnormal chest X-ray findings are commonly seen after lung resections.
14.8 Diagnosis
The actual incidence of postoperative pneumonia after thoracic surgery is
unknown. There is no gold standard for the diagnosis of postoperative
pneumonia so the incidence of pneumonia varies in the literature. Many centers
use only clinical criteria, whereas others use invasive diagnostic techniques.
Fever > 38 °C, leukocytosis (white blood cell count ≥12000cells/μL) or
leukopenia (white blood cell count ≤4000 cells/μL), purulent secretion, and new
or progressive consolidation on chest X-ray are parameters used when
pneumonia is suspected (Fig. 14.1). In addition to these criteria, dyspnea,
worsening oxygenation, and changes in the amount or character of sputum
support the diagnosis of pneumonia. Radiologic signs of pneumonia may be
difficult to differentiate pneumonia from pulmonary embolism or atelectasis,
especially in the immediate postoperative period. Chest X-rays are taken in the
ICU with portable machines, which also add difficulty resulting in suboptimal
quality images. The evaluation of chest X-rays is more difficult in patients who
undergo lung surgery, and for these reasons, chest X-rays are only used to
support the diagnosis; therefore thorax CT may be useful for definitive diagnosis
in this situation (Figs. 14.2 and 14.3).
Fig. 14.1 Chest X-ray showing pneumonia after the right pulmonary resection
Fig. 14.2 CT image of right pneumonia after the left pneumonectomy
Fig. 14.3 CT image of right pneumonia after the right pulmonary resection
Endotracheal aspiration cultures are mostly used for the diagnosis of

pneumonia. This is an inexpensive, easy, and quick method when compared with
bronchoscopic cultures. However, its accuracy is questionable in many respects;
distinguishing between infection and colonization is very difficult. If ETA
samples are quantitatively analyzed, the accuracy of the results is close to
bronchoscopic results.
Differential diagnosis in this period is quite difficult. Sputum samples should
be obtained if patients can cough effectively. For patients being treated in the
ICU and being mechanically ventilated, fiberoptic bronchoscopy is very
convenient. Bronchoscopic sampling should especially be performed in patients
who fail to respond to antibiotic treatment. Bronchoscopic sampling is
appropriate for rare microorganisms such as viral, fungal, and atypical etiologic
agents in patients who had induction therapy before surgery. Microorganisms
isolated from airways during the perioperative period may help to initiate
empiric antibiotic treatment.
14.9 Treatment
The empirical antibiotic treatment should be started based on patient factors,
local infection, and susceptibility patterns. If patients have no risk factors for
multidrug-resistant microorganisms (MDR) such as neoadjuvant therapy, longer
entubation time, and steroid therapy aminopenicillin (sulbactam/ampicillin or
amoxicillin/clavulanic acid), third-generation cephalosporin (cefotaxime) or
narrow-spectrum carbapenem (ertapenem) can be used. If patients have risk
factors for MDR, antipseudomonal cephalosporin (cefepime, ceftazidime), or
antipseudomonal carbapenem (meropenem, imipenem), β-lactam/β-lactamase
inhibitor (piperacillin/tazobactam) + antipseudomonal fluoroquinolone
(ciprofloxacin) or aminoglycoside (amikacin, gentamicin) can be used, and if
MRSA is suspected, vancomycin or linezolid should be used. Antibiotic therapy
is arranged according to culture results and patient clinical status. In recent years
there has been an increased incidence of resistance to Acinetobacter spp., which
should be taken into account because this bacteria is only susceptible to
colimycin.
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DOI 10.1007/978-3-319-19908-5_15
15. When and How Do I Have to Treat the

Arrhythmias After Thoracic Surgery?
Wilhelm Haverkamp1 and Thomas Hachenberg2
(1) Department of Cardiology, Charite University Medicine, Berlin, Germany
(2) Department of Anaesthesiology and Intensive Care Medicine, Otto-von-
Guericke University, Magdeburg, Germany

Thomas Hachenberg
Email: Thomas.Hachenberg@med.ovgu.de
15.1 Introduction
Cardiac arrhythmias are a common phenomenon affecting millions of people
worldwide. In more than 60 % of healthy adults, atrial and ventricular premature
beats can be detected on 24-h Holter monitoring [1]. In Europe, atrial fibrillation
is present in about 2–3 % of the population, and its prevalence is likely to
increase owing to widespread population aging [2]. Symptomatic bradycardia is
a frequent reason for permanent pacemaker implantation. Ventricular
extrasystoles are the most common type of arrhythmia that occurs after
myocardial infarction. Arrhythmias may occur at any age but are more common
among older people.
Since arrhythmias are common in the general population, it is not surprising
that they are also frequently observed in patients undergoing surgery, particularly
postoperatively. Some patients have a history of arrhythmias; in others, they
occur for the first time. New arrhythmias are a well-known complication after
surgery and may impact perioperative morbidity and mortality. This paper
summarizes the pathophysiology, risk factors, and the management of
arrhythmias in patients undergoing noncardiac thoracic surgery. Table 15.1 lists
the negative implications these arrhythmias have.
Table 15.1 Negative implications of postoperative atrial fibrillation
Increased mortality
Increased pulmonary complications
Hemodynamic deterioration and instability
Induction or exacerbation of heart failure
Increased mean lengths of intensive care unit and hospital stay
Increased mean hospital charges
15.2 Pathophysiology
The clinical manifestation of arrhythmias requires both the presence of a
vulnerable cardiac substrate and a trigger that initiates the arrhythmia. Changes
in myocardial structure and electrical function constitute the substrate for
arrhythmias. Examples for typical arrhythmia substrates are atrial fibroses
(favoring atrial fibrillation) and a post-myocardial infarction scar (promoting
ventricular tachycardia). The substrate is patient specific but may be modified by
the below discussed risk factors. The arrhythmia trigger is defined as a single
incident that may set off an arrhythmia. The trigger often takes the form of a
premature beat, but may also consist of acceleration or slowing of the heart beat
or myocardial stretch [3].
Many perioperative factors can be considered to affect both the arrhythmia
substrate and trigger, thereby increasing atrial and ventricular susceptibility to
arrhythmias. Risk factors can be classified into patient and surgery related (Table
15.2).
Table 15.2 Risk factors for perioperative arrhythmias, particularly postoperative atrial fibrillation
Patient-related risk factors

Increasing age
Male sex
Structural heart disease (coronary artery disease, valve disease, left ventricular hypertrophy, systolic and
diastolic left ventricular dysfunction)
Extracardiac risk factors (obesity, previous stroke, and concomitant lung disease)
Surgery-related risk factors
Surgical trauma (type of procedure/operation, magnitude of lung resection, dissection around the atria,
mechanical factors such as instrumentation)
Hemodynamic stress (volume overload or depletion, hypertension, endogenous catecholamines)
Metabolic changes (hypoxemia, hypercarbia, acid-base imbalances)
Electrolyte disturbances (particularly hypokalemia)
Drug effects (beta-blocker withdrawal, digoxin, exogenous catecholamines, phosphodiesterase inhibitors
(milrinone), levosimendan)
15.2.1 Patient-Related Risk Factors

Various patient-related clinical and nonclinical risk factors for postoperative
arrhythmias have been described. One of the most relevant patient-specific risk
factor is age. Increasing age has been demonstrated to be correlated with the
development of arrhythmias in the general population as well as in the
postoperative setting. Age-related structural and/or electrophysiological changes
appear to lower the threshold for atrial and ventricular arrhythmias in the elderly.
Since patients undergoing thoracic surgery present with a mean age of 67 years,
the risk for the development of arrhythmias is inherently increased [4].
Arrhythmias are most likely to occur in patients with structural heart disease.
Patients undergoing noncardiac thoracic surgery often have the substrate of atrial
enlargement or elevation in atrial pressures, which predispose to atrial
tachyarrhythmias. A history of arrhythmias predisposes to postoperative events.
Reported extracardiac risk factors for postoperative atrial tachyarrhythmias
include obesity, previous stroke, and history of chronic obstructive pulmonary
disease [5]. These risk factors are identical to those known to increase the
propensity to the development of atrial fibrillation in the nonsurgical setting.
15.2.2 Surgery-Related Risk Factors

Postoperative arrhythmias are a well-known problem during and after
cardiothoracic surgery; however they may also complicate major abdominal
surgery. The prevalence depends on the type of operation and the extent of
cardiac monitoring after surgery. The prevalence of postoperative arrhythmias
may range from 4 % of patients undergoing major general surgery, vascular, and
orthopedic surgery to 20 % in patients having elective colorectal surgery [6].
The trauma associated with surgical procedures predisposes patients to atrial
and ventricular arrhythmias. Inflammatory mechanisms have been proposed in
the development of postoperative arrhythmias since their incidence peaks at 2
to3 days after surgery [5]. Hemodynamic stress favoring arrhythmias may result
from surgical trauma, volume overload or depletion, hypertension, and increased
levels of endogenous catecholamines. Hypoxemia, hypercarbia, acid-base
imbalances, as well as mechanical factors such as instrumentation often
predispose to electrophysiological changes favoring the occurrence of
arrhythmias. Hypokalemia may provoke postoperative atrial and ventricular
arrhythmias [7].
Beta-blocker withdrawal has been associated with an increased rate of
postoperative supraventricular tachyarrhythmias. A state of heightened
catecholamine effect occurs because chronic beta-blocker use leads to a higher
density of beta-adrenergic receptors. Digoxin use has been described as a risk
factor for paroxysms of atrial fibrillation after surgery. The intravenous
administration of catecholamines and phosphodiesterase inhibitors such as
milrinone or enoximone and levosimendan has been reported to cause
ventricular premature beats, short runs of ventricular tachycardia, and atrial
fibrillation [5].
It is worth noting that the pathogenesis of postoperatively occurring atrial
and ventricular arrhythmias is often multifactorial; it involves some or all of the
mentioned mechanisms.
15.3 Atrial Fibrillation and Other Supraventricular

Arrhythmias
Isolated atrial premature beats are very common after thoracic surgery and are
often related to electrolyte or other metabolic imbalances. Atrial premature beats
are usually readily identified by surface ECG or continuous telemetric
monitoring. Paroxysmal supraventricular tachycardia develops in about 3 % of
patients undergoing general surgery. The most frequent sustained arrhythmia is
atrial fibrillation. The incidence varies widely (from 12 to 44 %) depending on
the type of surgery and patient characteristics. In an analysis of 2588 patients
undergoing noncardiac thoracic surgery, the incidence of postoperative atrial
fibrillation was 12.3 % [8]. In a multivariate analysis, significant risk factors for
the occurrence of atrial fibrillation were male sex (relative risk (RR) 1.72),
advanced age (RR in patients with age 70 or grater 5.3), a history of congestive
heart failure (RR 2.51), a history of arrhythmias (RR 1.92), a history of
peripheral vascular disease (RR 1.65), resection of mediastinal tumor or
thymectomy (RR 2.36), lobectomy (8.91), bilobectomy (7.16), pneumonectomy
(8.91), esophagoectomy (2.95), and intraoperative transfusions (1.39) [9].
Patients with atrial fibrillation have longer mean intensive care unit and
hospital stays. Mean hospital charges are more than 30 % higher when compared
with patients without atrial fibrillation. Importantly, an increased mortality in
patients with postoperative atrial fibrillation has been demonstrated [10].
However, since many patients with postoperative atrial fibrillation have complex
comorbidities, it is not clear to what extent the arrhythmia itself contributes to
this increase in mortality [4].
With the aim to facilitate preoperative risk stratification, thoracic surgical
procedures were recently divided into low- (<5 %), moderate- (5–10 %), and
high- (>15 %) risk groups based on their expected incidence of postoperative
atrial fibrillation (Table 15.3). In moderate- and high-risk patients, extended
ECG monitoring is recommended (e.g., postoperative telemetry for 48–72 h) [11,
12].
Table 15.3 Risk stratification of thoracic surgery procedures for their risk of postoperative atrial fibrillation
Low-risk procedures Intermediate-risk High-risk procedures
(<5 % incidence) procedures (>15 % incidence)
(5–15 % incidence)
Flexible bronchoscopy with and without biopsy Thoracoscopic Resection of anterior
Photodynamic therapy sympathectomy mediastinal mass
Tracheal stenting Segmentectomy Thoracoscopic lobectomy
Placement of thoracostomy tube or PleurX catheter Laparoscopic Nissen Open thoracotomy for
(CareFusion Corporation, San Diego, California) fundoplication/myotomy lobectomy
Pleuroscopy, pleurodesis, decortication Zenker diverticulectomy Tracheal resection and
Tracheostomy reconstruction/carinal
resection
Rigid bronchoscopy
Pneumonectomy
Mediastinoscopy
Pleurectomy
Thoracoscopic wedge resection
Volume
Bronchoscopic laser surgery
reduction/bullectomy
Esophagoscopy/PEG/esophageal dilation and/or
Bronchopleural fistula
stenting
repair
Clagett window
Lung transplantation
Esophagectomy
Pericardial window
Atrial premature beats usually do not need specific treatment. Paroxysmal

supraventricular tachycardia occurs from time to time and treatment is often
simple. If vagal maneuvers are not successful, adenosine can be used in
increasing doses (Table 15.4). Success rates exceed 95 %. Electrical
cardioversion is rarely needed. The management of atrial fibrillation is much
more complex.
Table 15.4 Drugs used for postoperative arrhythmias
Drug Dosing Indication Side effects
Adenosine 6 or 12 mg, the 18 mg as an iv Paroxysmal SVT Transient heart block, flushing, chest
bolus pain, induction of AF (rare)
Atropine 0.4–1 mg iv Bradycardia or AV Excessive tachycardia
block
Verapamil 5–10 mg iv Rate control of AF, Hypotension, exacerbation of CHF, AV
paroxysmal SVT block
Diltiazem 10–20 mg iv bolus, then Rate control of AF, Hypotension, exacerbation of CHF, AV
infusion at 5–15 mg/h paroxysmal SVT block
Esmolol 0.5 mg/kg bolus and infusion at Rate control of AF Hypotension, bronchospasm,
0.05 mg/kg/h; increase by 0.05 exacerbation of CHF
mg/kg/h every 5 min
Metoprolol 5 mg iv every 5 min × 3 Rate control of AF Hypotension
Digoxin 0.25 mg iv every 4–6 h up to 1 Rate control of Delayed onset, nausea, vomiting
mg persisting AF
Amiodarone Prophylaxis, 300 mg iv, then Rate control and Hypotension, bradycardia abnormal
600 mg orally for 3–5 days; conversion of AF, QTc prolongation with torsade de
treatment, 150 mg iv over 10 frequent non- pointes (rare), acute respiratory distress
min, then 1 mg/min × 6 h, then sustained/sustained syndrome (rare, after supra-therapeutic
0.5 mg/min VT, VF doses)
AF atrial fibrillation, CHF congestive heart failure, SVT supraventricular

tachycardia, VT ventricular tachycardia, VF ventricular fibrillation
15.3.1 Treatment of Atrial Fibrillation

Given the often transient nature of new-onset postoperative atrial fibrillation (the
arrhythmia frequently resolves within 4–6 weeks), the control of the ventricular
response rate is usually the initial therapy. Conventionally, nondihydropyridine
calcium channel antagonists (verapamil and diltiazem) and digitalis have been
used for treating postoperative atrial fibrillation (Table 15.4) [11, 12]. However,
since calcium antagonists may be associated with hypotension and are
contraindicated in patients with heart failure, they may not be the ideal drugs in
patients with compromised heart function. The same is true for digitalis, which
acts primarily by increasing vagal tone. The effects of digitalis are attenuated
postoperatively when sympathetic tome is markedly increased. Beta-blockers
have been shown to be effective when atrial fibrillation occurs after surgery.
Patients taking beta-blockers before surgery should have beta-blockade
continued; abrupt withdrawal is associated with an increased risk of
complications and should be avoided. Amiodarone iv should be preferred in
patients with known severe systolic dysfunction. The drug also exerts
antiarrhythmic effects, which may lead to the termination of the arrhythmias. A
prospective, randomized, controlled, double-blinded study included 254 patients
undergoing thoracic surgery for lung cancer. The patients received either 300 mg
of amiodarone or placebo intravenously after surgery and an oral dose of 600 mg
or placebo twice a day for 5 postoperative days. Amiodarone significantly
decreased the prevalence of atrial fibrillation (38 patients (placebo group) vs. 11
patients (amiodarone group)). A number needed to treat of 4.4 (3.1–7.8) was
calculated and adverse events occurred equally in both study arms (total of ten
patients) [13].
Acute pulmonary toxicity has been reported with amiodarone in patients
undergoing lung resection. Amiodarone or at least high amiodarone doses
(>1000 mg/day) should be avoided in these patients. Preexisting pulmonary
disease is associated with an increased risk of amiodarone pulmonary toxicity
[14].
Class I antiarrhythmic drugs (sodium channel blockers like flecainide and
propafenone) may be used in patients without structural heart disease. However,
even in those patients, these agents may exert proarrhythmic effects (e.g.,
convert well-tolerated atrial fibrillation compromising atrial flutter).
Immediate electrical cardioversion is indicated in patients who demonstrate
severe hemodynamic deterioration in response to new-onset atrial fibrillation. It
is highly effective (>90 % conversion rate). However, early recurrences are
frequent. Cardioversion from well-tolerated postoperative atrial fibrillation is
usually not necessary because of a frequent self-limited course. New atrial
fibrillation after thoracic surgery often resolves within 4–6 weeks, regardless of
treatment.
Patients who develop atrial fibrillation after surgery are at risk of
thromboembolic events, including stroke. In the individual postsurgical patient
with an embolic event, the cause may be unclear, as underlying comorbidities are
often responsible for such strokes, rather than the arrhythmia itself. However,
based on evidence that anticoagulant therapy prevents episodes of systemic
embolization in the broad population of patients with atrial fibrillation,
anticoagulation seems reasonable in patients with postoperative AF who have
stroke risk factors (age > 65, female gender, prior stroke, hypertension,
congestive heart failure diabetes). However, a reduction of events with
anticoagulant therapy in this population has never been well studied.
15.3.2 Prevention of Atrial Fibrillation

Several strategies to prevent postoperative atrial fibrillation have been studied.
In daily practice, the most widely used prophylactic therapy seems to be the
administration of beta-blockers. Prophylactic beta-blocker administration
reduces the incidence of postoperative atrial fibrillation by about 50 % [15]. The
greatest benefits are seen when beta-blockers are initiated some time prior to
surgery. Contraindications need to be carefully considered. Amiodarone
significantly lowers the incidence of postoperative atrial fibrillation. The
prophylactic potency seems to be comparable with that of beta-blockers. It is
worth reminding the rare complication of intravenous amiodarone, the onset of
acute respiratory distress syndrome in the postoperative period in patients
undergoing lung resection. In one randomized study, magnesium iv was effective
in reducing the incidence of postoperative atrial fibrillation. However, these
results have never been confirmed by other studies.
Thoracic epidural analgesia (TEA) with bupivacaine has been shown to
decrease the prevalence of atrial fibrillation after lung resection surgery [16].
However, a retrospective matched pair analysis could not confirm these results.
A cohort of 1,236 patients undergoing resections was included into the study:
937 received a combination of general anesthesia and TEA (TEA) and 299
received general anesthesia only (non-TEA). After matching 311 TEA patients
and 132 non-TEA patients, no differences on the occurrence of postoperative
atrial arrhythmia could be demonstrated [17]. Thus, the role of central neuraxial
analgesia for the prevention of postoperative atrial fibrillation is unclear.
To the knowledge of the authors, no systematic data are available that have
evaluated how different institutions use prophylactic drug administration for the
prevention of postoperative atrial fibrillation. The own experience suggests that
atrial fibrillation prophylaxis is not a routine. Most institution try to optimize all
aspects of perioperative care thereby minimizing the arrhythmia risk [18].
15.4 Ventricular Arrhythmia

Isolated ventricular premature betas documented postoperatively do not indicate
an increased risk for the development of malignant ventricular tachyarrhythmias
(i.e., sustained ventricular tachycardia, ventricular fibrillation), and, therefore,
there is no need for treatment. Non-sustained and sustained ventricular
tachyarrhythmias are rare. Reported incidences after surgery range from 0.5 to
1.5 %. Ten most patients developing theses arrhythmias have severe heart
disease with depressed left ventricular function or suffer from severe acute
postoperative complications (e.g., hemodynamic instability, myocardial
ischemia, septic shock, major surgical complications).
When frequent and complex premature beats and non-sustained ventricular
tachycardia occur, the correction of any reversible cause of arrhythmias (see
above) should be pursued. Antiarrhythmic drugs may be indicated when longer
repeated episodes of non-sustained or sustained ventricular tachycardia develop.
The preferred antiarrhythmic drug is amiodarone administered intravenously
[14]. Class I antiarrhythmic drugs have also been used successfully (e.g.,
lidocaine); however, in this setting, they are also associated with an increased
risk for ventricular proarrhythmia. In the case of hemodynamic deterioration due
to sustained ventricular tachyarrhythmias, either R-wave triggered DC
cardioversion (in the case of hemodynamically well-tolerated ventricular
tachycardia) or, after hemodynamic collapse due to unstable ventricular
tachycardia or ventricular fibrillation, immediate defibrillation and
cardiopulmonary resuscitation may become necessary [10].
Most patients with known, previously documented ventricular
tachyarrhythmias do have an implanted cardioverter/defibrillator. These devices
are effective in terminating spontaneous arrhythmia, even in the postoperative
setting. All devices should be thoroughly evaluated before and after surgery to
make sure that its function has not been damaged or changed. If electrocautery is
to be used, pacemakers should be placed in a triggered or asynchronous mode;
implantable cardioverters should have arrhythmia detection suspended before
surgery.
15.5 Bradyarrhythmias
Bradyarrhythmias are common after cardiac surgery (particularly after valve
surgery), but are relatively rare after noncardiac thoracic surgery [19]. In the
majority of cases, they consist of transitory episodes of low ventricular heart rate
resulting from (usually preexisting) sick sinus syndrome or various degrees of
atrioventricular blocks. They often result from increased vagal tone caused by an
intervention, such as spinal or epidural anesthesia, laryngoscopy, or surgical
intervention. Bradyarrhythmias may gain hemodynamic relevance because of a
decrease in cardiac output [19]. Atropine can reverse symptomatic bradycardia.
It is prudent to stop all unnecessary medications that can cause increased AV
block like beta-blockers or calcium channel blockers. Temporary electrical
pacing may be required in symptomatic bradycardias not responding to atropine.
In some cases, when the conduction defect does not revert, permanent pacing
may be necessary.
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DOI 10.1007/978-3-319-19908-5_16
16. Management of Antiaggregated and

Anticoagulated Patients Scheduled for
Thoracic Surgery: Recommendations for
Venous Thromboprophylaxis
Juan V. Llau1, 2, Manuel Granell3, 2, 4 and Mª José Jiménez5
(1) Department of Anaesthesia and Critical Care, Hospital Clínic, Valencia.
(2) University of Valencia, Valencia, Spain
(3) Department of Anaesthesiology, Critical Care and Pain Relief, General
University Hospital of Valencia, Valencia, Spain
(4) Catholic University of Valencia, Valencia, Spain
(5) Department of Anaesthesiology, Critical Care and Pain Relief, Hospital
Clinic of Barcelona, Barcelona, Spain

Manuel Granell
Email: mgranellg@hotmail.com
16.1 Introduction
Thoracic surgery is performed in many cases in patients that are under the effect
of some drugs. Most common drugs are, probably, antiplatelet (APA) and
anticoagulant (AC) agents. The management of these patients is a common
challenging problem and a cause of frequent assessment from thoracic surgeons.
These patients could require temporary interruption of the administration of the
antiplatelet or anticoagulant drug or could need to receive a new anticoagulant
for thromboprophylaxis in the perioperative period. So, it is necessary to balance
the risk of a thromboembolic event during the possible interruption of the
therapy with the risk for bleeding if the antithrombotic drug is administered
close to surgery.
In this chapter, current guidelines for the management of these patients are
revised.
16.2 Antiplatelet Agents and Thoracic Surgery

It is very common that patients who are scheduled for thoracic surgery are
treated with APA due to their wide indications and the characteristics of these
patients. They are drugs of diverse origin, whose prophylactic and therapeutic
effects are especially important in the prevention and treatment of the arterial
thrombosis. The most common APAs used as chronic treatment are
cyclooxygenase inhibitors such as aspirin and adenosine diphosphate receptor
P2Y12 antagonists such as clopidogrel or prasugrel; new antiplatelet agents
include ticagrelor and cilostazol. Their main characteristics are shown in Table
16.1 [1–4].
Table 16.1 Main characteristics of some current antiplatelet agents
Drug Mode of action Half-life Onset of action Duration
of action
Aspirin Irreversible inhibition of the enzyme 15–20 min Few minutes Platelet
COX-1 lifespana
Clopidogrel Irreversible binding to the ADP P2Y12 About 8 h (active 2 h if given Platelet
receptor of the platelets metabolites after liver loading dose lifespana
action)
Prasugrel Irreversible binding to the ADP P2Y12 Fast conversion in About 30 min Platelet
receptor of the platelets active metabolites lifespana
Ticagrelor Reversible P2Y12 antagonist Approximately 12 h About 30 min 4–5 days
after a loading
dose
Cilostazol Selective inhibition of phosphodiesterase Around 21 h 2–3 h 12–48 h
IIIA (reversible inhibition of platelet
aggregation)
aFor the recovery of haemostatic competence, the recovery of the function of all
platelets could not be necessary. So, 5 days after the last administration of the
majority of these antiplatelet agents could be enough
Although the management of the APA in the perioperative period is not easy,
the main challenge for the anaesthesiologist and the thoracic surgeon is those
patients receiving an APA with a coronary stent (mainly, drug-eluting coronary
stents).
16.2.1 Rationale for the Recommendations

Some years ago, the most common practice with the APA was their withdrawal
between 7 and 10 days before thoracic surgery. But, in the last years, several
general documents recommending the maintenance of the APA have been
published, whenever the haemorrhagic risk allows this continuation [1–7].
The perioperative management of APA must be based on the optimal
assessment of benefit/risk relationship. This includes the stratification of the
perioperative haemorrhagic risk associated with the continuation of antiplatelet
agents throughout surgery and the stratification of the thrombotic risk associated
with their discontinuation. In order to summarise all the information, you can
find a summary in Table 16.2 [2, 4–8].
Table 16.2 Proposed stratification of the haemorrhagic risk related with the continuation of antiplatelet
agents through the perioperative period and the thrombotic risk associated with their discontinuation
Haemorrhagic Minor Moderate Major

risk
Transfusion usually not needed Transfusion usually Possible bleeding in an
Minor plastic/general/OS needed enclosed space
surgery Cardiac surgery Cranial surgery, spinal surgery,
Biopsies, tooth extraction, Major surgery of the posterior
surgery of the anterior segment OS/visceral/ENT/urology segment of eye. Transurethral
of eye or reconstructive surgery prostatectomy
Thrombotic Minor Moderate Major
risk
>6 months after AMI, CABG, >12 months after DES <12 months after DES
percutaneous coronarography, 6–24 weeks after AMI, <6 weeks after AMI, CABG,
BMS, coronary surgery, CVS CABG, BMS, CVS BMS, CVS
(>12 months if high-risk patient (6–12 months if high-risk (<6 months if high-risk patient
or associated complications) patient or associated or associated complications)
complications)
OS orthopaedic surgery, ENT ear-nose-throat surgery, AMI acute myocardial

infarction, CABG coronary artery bypass grafting, BMS bare-metal stent, DES
drug-eluting stent, CVS cerebrovascular stroke
16.2.2 General Recommendations for Patients Scheduled

for Thoracic Surgery
The practical guidelines for the management of APA on patients scheduled for
elective thoracic surgery need the local agreement of a multidisciplinary team
that includes anaesthesiologists and thoracic surgeons, with the participation and
acceptance by haematologists, cardiologists and neurologists.
The decision to discontinue the antiplatelet therapy prior to surgery should be
based on careful cardiovascular and thrombotic risk assessment of the patient
and on the type of surgery and of bleeding risk. The recommendations about the
perioperative management of antiplatelet therapy in these patients are not fully
agreed, but they can be summarised as follows [1–8]:
In all cases, it is recommended that a low dose of aspirin (75–100 mg) be
maintained throughout the perioperative period, unless the risk of bleeding
clearly outweighs thrombotic risk.
In order to reduce the potential risk of bleeding, aspirin dose higher than
200 mg should be replaced by 75 or 100 mg.
The treatment should be substituted by low-dose aspirin in the case of
patients treated with clopidogrel as monotherapy and where discontinuation
is mandatory (unless contraindicated).
If antiplatelet therapy must be discontinued, it should be stopped the
shortest time possible: 2 days for aspirin and 5 days for clopidogrel.
Thereafter, treatment should be restarted as soon as possible following
surgery after ensuring haemostasis, between 6 and 48 h during the
postoperative period. Depending on the withdrawal time and in order to
accelerate antiplatelet response, loading dose administration may be
indicated as follows: aspirin 250 mg and clopidogrel 300 mg.
16.2.3 Current Antiplatelet Protocols in Patients with

Drug-Eluting Stents
APAs are recommended in the treatment of patients who had undergone
percutaneous coronary interventions (PCI) and have a coronary stent in place.
After this, the current protocols of administration of APA could be summarised
as follows [9]:
After stent implantation, the use of aspirin should be continued indefinitely.
It is reasonable to use aspirin around 100 mg per day in preference to higher
maintenance doses.
The duration of the therapy with a thienopyridine after stent implantation
should generally be given for at least 12 months. Options could include
clopidogrel 75 mg daily, prasugrel 10 mg daily and ticagrelor 90 mg twice
daily.
If the risk of morbidity from bleeding outweighs the anticipated benefit
afforded by a recommended duration of thienopyridine therapy after stent
implantation, earlier discontinuation (e.g. <12 months) of thienopyridine
therapy is reasonable.
Continuation of clopidogrel, prasugrel or ticagrelor beyond 12 months may
be considered in patients undergoing placement of drug-eluting stent.
From this protocol in the treatment of patients with a coronary stent in place,
the recommendations for their management have some special considerations
[1–4, 7–10]:
Although there is not a valid algorithm for all situations, current trend is to
delay all surgery that is not life threatening if the stent has high thrombotic
risk. So, elective noncardiac surgery should not be performed in the 4–6
weeks after a bare-metal stent implantation or the 12 months after drug-
eluting stent implantation in patients in whom the thienopyridine will need
to be discontinued perioperatively. In spite of this recommendation, the
evidence supporting this practice is scarce and limited, and major adverse
cardiac events (MACE) in this kind of patients undergoing surgery could be
related more with emergency surgery and advanced cardiac disease but not
with stent type or timing of surgery beyond 6 months after stent
implantation [11].
If surgery can’t be delayed, the continuation of the antiaggregation is
essential to minimise the thrombotic risk of the stent. If it is not possible to
maintain the APA due to a high bleeding risk, it is necessary to know that
the withdrawal of the thienopyridine and the maintenance of the aspirin
alone do not assure the elimination of the thrombotic risk. So the final
decision in cases of surgeries that it is not possible to be delayed should be
multidisciplinary and made individually.
In all cases, the administration of the APA treatment after surgery should be
done as soon as possible. Main recommendation is to give it in the first 24 h
after the end of surgery if the haemostatic competence of the patient is
assured.
After the high-risk period, if the surgery is likely to cause little or no risk of
bleeding, it is recommended not to stop antiplatelet therapy. Moreover, in
general, the maintenance of the treatment with aspirin in patients with a
coronary stent in place is the first option.
For patients with a coronary stent who must undergo urgent surgical
procedures that mandate the discontinuation of dual antiplatelet therapy, it
is reasonable to continue aspirin if possible and restart the thienopyridine as
soon as possible in the immediate postoperative period.
16.3 Management of Anticoagulated Patients Scheduled

for Thoracic Surgery
Many patients receive oral and chronic anticoagulation due to atrial fibrillation
or a mechanical heart valve, although other indications for it include
cerebrovascular pathology (repeated strokes) or prevention of recurrences of
previous thromboembolic events. Nowadays, the anticoagulant therapy could be
made by vitamin K antagonists (VKAs) or by any of new direct oral
anticoagulants (DOACs), such as dabigatran, rivaroxaban, apixaban or
edoxaban, which are recently accepted or waiting their approval for these
indications.
16.3.1 Management of Patients Under Vitamin K

Antagonists
The perioperative management of VKAs is well established, and nearly no
change has been done in the lately recommendations [2, 12–15]. Rational
decisions are made depending on the risks of thrombosis and bleeding associated
with the different alternatives. In general the interruption of VKAs is required to
achieve normal or near-normal haemostasis at the time of surgery (INR 1.5 or
below). After stopping VKAs, between 3 and at least 5 days will be required for
most anticoagulant effect to be eliminated (with acenocoumarol 3 days seem to
be enough, and with warfarin the delay should be up to 5 days). So, the main
recommendation in patients scheduled for thoracic surgery that require
temporary interruption of a VKA before the operation is to stop VKAs
approximately 5 days before surgery in the case of warfarin [2], although with
acenocoumarol, the recommended time could be shorter (3 days). After surgery,
it is recommended resuming VKA 12–24 h postoperative, when oral intake is
permitted and there is adequate haemostasis.
The temporary discontinuation of VKAs could expose patients to a risk of
thromboembolism, although some controversies have been published for this
topic [14–18], mainly for a possible tendency to increase bleeding with the
bridging therapy without any decrease of thrombotic events. In general, current
protocols recommend:
For patients with a mechanical heart valve, atrial fibrillation or VTE at high
risk for thromboembolism, there is a need of bridging anticoagulation
(administration of a short-acting anticoagulant) during the interruption of
VKA therapy.
For patients at low risk for thromboembolism, the bridging can be avoided.
When there is a moderate risk for thromboembolism, the bridging or no-
bridging approach chosen should be based on an assessment of individual
patient- and surgery-related factors. If the surgery or procedure is a low risk
for bleeding, the bridging may be considered, but if it is of high bleeding
risk (major thoracic surgery), no bridging therapy may be better.
The best option for bridging therapy is, probably, the administration of sc
LMWH. Again, the dose of the LMWH in this scenario is controversial, and the
proposals go from prophylactic doses to therapeutic ones (high doses reserved
only for patients at high thrombotic risk). In any case, the last dose should be
given before surgery time, ensuring normal haemostasis (around 24 h for
LMWH). After surgery, therapeutic-dose LMWH should be resumed 24 h
postoperatively in non-high-bleeding-risk surgery. In patients who are
undergoing high-bleeding-risk surgery, the resumption of therapeutic-dose
LMWH should be delayed 48–72 h after surgery.
16.3.2 Management of Patients Under Direct Oral

Anticoagulant
DOACs have in common that they are given orally and they do not need
antithrombin for their action, but they are different drugs acting in different
targets of the coagulation cascade: rivaroxaban, apixaban and edoxaban directly
inhibit factor Xa; dabigatran is a direct inhibitor of factor IIa.
They can be used for thromboprophylaxis in patients scheduled for major
orthopaedic surgery (total hip or knee arthroplasties), for the prevention of a
stroke in patients with atrial fibrillation and for the treatment and secondary
prevention in patients with venous thromboembolism [19].
As there is no experience enough about the perioperative management of
DOACs, it is necessary to highlight some points:
Some antidotes have been developed for their reversal: idarucizumab for
the reversal of dabigatran [20] and andexanet for the antagonization of
xabans [21]. If the antidotes are not availables, some papers propose the
adminsitration of PCC for the first line control of severe bleeding related
with the administration of DOACs [19].
The dosage used for the chronic anticoagulation is quite different and
higher than the dosage used for thromboprophylaxis.
The safety objective to be reached in patients receiving DOAC for “full”
anticoagulation is, in these days, unknown. The safe preoperative objective
has been defined for <30 ng/ml in any DOAC [22], but it is very difficult to
control plasma levels in current practice. Moreover, there is a lack of
relation between this plasma level and the results of standard coagulation
tests.
Main objective for their management in patients scheduled for thoracic
surgery must be the safety, considered as haemorrhage associated to the
procedure. Of course, the necessary antithrombotic protection should be in
mind.
With these highlighted points, main recommendations for the management of
DOAC in the perioperative period of a thoracic surgery could be divided in [23]:
Bridging strategy. Stop the anticoagulant 4–5 days before surgery and make
the bridging with LMWH, as if it was AVK. This possibility has been
proposed by the French [24] and the Spanish anaesthesiology societies [25].
It could be the best one (the most safe one) to manage the three DOACs as
one, mainly for selected patients at high thrombotic risk (defined as a
CHA2DS2-VASc score more than 4 [26] or CHADS2 more than 2 [27]). In
a similar way it occurs with VKAs, the dosage of the LMWH will be based
on the thrombotic risk of the patient. Nevertheless, this strategy has been
abandonned by most groups.
No bridging strategy. Stop the drug before surgery without the
administration of LMWH during the window period. Based on DOAC rapid
onset of action and short half-life, it has been proposed their withdrawal
some days before surgery [28]. As DOACs have different half-lives and
different renal clearance rates, this proposal should be adapted to each drug,
to the patient, to the creatinine clearance and to the procedure’s bleeding
risk. Nevertheless, there is no consensus on the “exact” time for this
management. Moreover, the lack of experience and data in patients
undergoing high-bleeding-risk procedures (complex thoracic procedures
with lung resection) demands to be extremely careful in these scenarios.
The Spanish forum, after recent article revisions and large discussions, has
proposed an easy and practical protocol, summarised in Table 16.3 [8, 25–27,
29–31]. The bridging therapy is also reflected as an option in this decision
algorithm, only for patients at high thrombotic risk.
Table 16.3 Proposed preoperative discontinuation time of direct oral anticoagulants based on renal function
and bleeding risk
Suggested minimal time from last intake before surgery
Drug Apixaban Dabigatran
CrCl (ml/min) Rivaroxaban
>50 30–50 >50 30–50
Low bleeding riska 1 d 2 d 2 d 3 d
Moderate to severe bleeding risk 2 d 3 d 3 d 4 d
High thrombotic risk Bridging therapy with LMWH is suggested
aIn patients with normal renal function undergoing “very low bleeding risk”
procedures, the direct oral anticoagulant may not be interrupted. In the case of
apixaban and dabigatran (both given twice per day), last dose before surgery
should be skipped
16.4 Thromboprophylaxis in Thoracic Surgery

Pulmonary embolism (PE) and deep vein thrombosis (DVT) are two clinical
presentations of venous thromboembolism (VTE) and share the same
predisposing factors, being PE in most cases a consequence of DVT. VTE is
currently regarded as the result of the interaction between patient-related and
setting-related risk factors. Patient-related predisposing factors are usually
permanent, whereas setting-related predisposing factors are more often
temporary. Patient-related predisposing factors include age, history of previous
VTE, active cancer, neurological disease with extremity paresis, medical
disorders causing prolonged bed rest (such as heart or acute respiratory failure)
and congenital or acquired thrombophilia, hormone replacement therapy and oral
contraceptive therapy [32–36].
During the perioperative period, VTE is a frequent and yet relatively
preventable cause of postoperative morbidity and mortality. Although the
benefits of thromboprophylaxis are broadly recognised in this context, the
recently proposed objective is to offer a tailored, procedure-specific, patient-
specific regimen, case-per-case decided.
16.4.1 Methods for Thromboprophylaxis

Methods used for thromboprophylaxis in surgical patients include general
measures and mechanical and pharmacological methods.
General measures include mobilisation and leg exercises. Adequate
hydration should be ensured in immobilised patients.
Mechanical methods increase mean flow velocity in leg veins and reduce
venous stasis. They include graduated compression stockings (GCS),
intermittent pneumatic compression (IPC) devices and pneumatic foot
pumps (PFP).
Pharmacological methods are necessary when the thrombotic risk is
moderate to high. They include low-molecular-weight heparins (LMWHs)
that are the most extended drugs used for thromboprophylaxis. Other drugs
available for thoracic surgical patients when indicated are fondaparinux,
unfractionated heparin (UFH) and antivitamin K drugs (VKAs)
(warfarin/acenocoumarol).
16.4.2 Rationale for Thromboprophylaxis in Thoracic

Surgery
The rationale for the use of thromboprophylaxis in patients admitted to a hospital
is based on solid principles and scientific evidence, including [34, 35, 37]:
High prevalence of VTE among hospitalised patients, because almost all of
them have one or more risk factors for VTE. If no prophylaxis is given, the
risk to develop any kind of VTE is highly variable, in dependence of the
medical/surgical condition of the patient.
Adverse consequences of unprevented VTE, mainly symptomatic DVT or
PE, fatal PE and post-thrombotic syndrome.
Efficacy of thromboprophylaxis, with a good cost-effectiveness relation of
pharmacological and mechanical methods.
Based on these points, it is recommended that all patients are assessed on
their thrombotic risk, balanced against their bleeding risk. The final decision
about the optimal thromboprophylaxis protocol to be administrated should be
made after the consideration of both risk factors. In general, patients at moderate
or high VTE risk with low to moderate bleeding risk should receive
pharmacological thromboprophylaxis. When such patients have a high bleeding
risk, they should receive mechanical thromboprophylaxis (preferably with IPC),
beginning with the administration of an antithrombotic drug when the bleeding
risk decreases [34, 35, 37, 38].
This rationale can be applied to patients scheduled for thoracic surgery,
having in mind that:
Many patients scheduled for thoracic surgery have a high risk for
perioperative VTE because of active cancer, age, preoperative
chemotherapy, complex major surgery, long surgical time, etc. Active
cancer is not uncommon between patients scheduled for thoracic surgery.
Only this condition must move to the clinician to consider the application of
the high-risk protocol for thromboprophylaxis during the perioperative
period, although the bleeding risk should be also considered.
It is suitable to stratify the VTE risk in each patient using a validated model
such as the Caprini score [39] which includes measures such as age,
type/duration of surgery, obesity, history of VTE or thrombophilia, presence
of a central venous catheter and malignancy. Between non-oncologic
patients, the risk stratification of thoracic surgical ones based on the Caprini
score classifies them in low-/intermediate-risk patients, so in most cases the
use of only mechanical prophylaxis methods is enough.
Most protocols include as the first option for pharmacological
thromboprophylaxis the LMWH [34–37], but some controversies have been
issued related with the moment of its initiation. There are no differences reported
in the literature in efficacy and safety between pre- or postoperative
administration of the first dose of LMWH, and the guidelines leave each one to
do their preference [40–42]. Nevertheless, the current tendency is to begin the
thromboprophylaxis in the postoperative period (most drugs can be given only
after surgery), and if the chosen drug is an LMWH administrated once daily, the
agreement is to start between 6 and 12 h after the end of surgery.
From this basis and the recent recommendations published in some
guidelines [34–37], we can summarise some suggestions for thromboprophylaxis
in thoracic patients (Table 16.4).
Table 16.4 Suggested thromboprophylaxis in thoracic surgical patients
Patient group Suggested thromboprophylaxis Suggested duration
options
Low risk for VTE (Caprini score 0–1) Early deambulation –
Moderate risk for VTE (Caprini LMWH or UFH or IPC/GCS 7–10 days (if pharmacological
score: 2–3) and not at high risk for (preferably IPC) prophylaxis) or until
bleeding discharge
High risk for VTE (Caprini score: 4 LMWH or UFH 7–10 days
or more) and not at high risk for IPC/GCS (preferably IPC) should (in cancer patients, consider
bleeding be added to pharmacologic prolongation up to 4 weeks)
prophylaxis
Moderate or high risk for VTE and IPC/GCS (preferably IPC) 7–10 days (if pharmacological
high risk for bleeding Initiate LMWH or UFH when prophylaxis) or until
bleeding risk diminishes discharge
(in cancer patients, consider
prolongation up to 4 weeks)
VTE venous thromboembolism, LMWH low-molecular-weight heparin, UFH

unfractioned heparin, IPC intermittent pneumatic compression, GCS graduated
compression stockings
16.4.3 Thromboprophylaxis in the Perioperative Period:

Implications for the Anaesthesiologist
The performance of regional anaesthesia, particularly epidural technique that is
specially indicated in this kind of surgery for postoperative analgesia, seems safe
in patients receiving anticoagulant drugs for thromboprophylaxis if there is an
appropriate management based on safety intervals suited to the type of
anaesthetic-analgesic technique to be carried out and particularly to the
characteristics of the drug [42, 43]. Nevertheless, the final decision to perform
regional anaesthesia in patients receiving drugs that affect haemostasis has to be
taken after careful assessment of individual risks and benefits, mainly in patients
receiving one anticlotting drug for thromboprophylaxis plus one antiplatelet drug
for any other medical indication [42, 43].
Main recommendations for the performance of neuraxial anaesthesia from
the last guideline of the European Society of Anaesthesiology [42] can be
summarised as follows:
Low-dose aspirin does not need to be stopped.
If clopidogrel cannot be stopped at least 5 days before surgery (ideally, 7
days), the performance of an epidural technique is not recommended.
Prophylactic doses of an LMWH are safe if the delay between its
administration and the performance of the neuraxial block is, at least, 10–12
h. If the first dose of LMWH is administrated after surgery, the delay
between the epidural block and the LMWH administration should be at
least 6–8 h. Finally, the epidural catheter should not be removed till 12 h
has passed since the last dose of LMWH.
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DOI 10.1007/978-3-319-19908-5_17
17. Pain Management Following Thoracic

Surgery
Mukadder Orhan Sungur1 and Mert Şentürk1

Mert Şentürk
Email: senturkm@istanbul.edu.tr
17.1 Introduction
There are numerous articles with the keywords “pain after thoracotomy” or
“postthoracotomy analgesia” emphasizing the fact that this is one of most
attractive and challenging topics of anesthesiology even after decades and
thousands of studies.
Several reasons contribute to this “ongoing challenge”:
1. Thoracotomies (with posterolateral and posterior incisions) are one of the

most painful operations. Physiopathology of postthoracotomy pain is very
complicated and still not totally explained.
2. The main target organ of the complications of postoperative pain and the
operation is the same: the lung. Therefore, there is a strong relationship
between appropriate postoperative pain therapy and pulmonary
complications like atelectasis and pneumonia [1].
3. Pain following thoracic surgery is triggered by breathing cycle constantly

and exacerbated by movements such as coughing or deep breathing which
can also determine efficacy of analgesic therapy [2]. Although a patient can
sleep without pain (i.e., “low VAS-rest”), optimal pain therapy targets
analgesia of a patient who can cough effectively (i.e., “low VAS-cough”).
However, achieving such a target with high doses of opioids can also worsen
the postoperative respiratory functions.
4. Last, but not least, thoracotomy is the second (after amputation) operation
which is most commonly associated with a “chronic postoperative pain
syndrome” [3, 4].
17.2 Physiology of Pain

Before discussing management of pain, a thorough understanding of pain
physiology and surgical trauma is a must. Acute pain after thoracotomy can be
due to direct or indirect trauma. Surgical dissection of tissues including skin,
muscles, ribs, pulmonary parenchyma, pleura, and nerves (acute intercostal
neuralgia) constitutes direct trauma. Stretching of ligaments (acute
costochondritis, posterior costochondral ligament damage, costochondral
dislocation), pressure exerted by rib retractors, and irritation or inflammation as
a result of surgery can cause indirect trauma [5, 6]. Trauma can continue even
after surgery due to drainage tubes, residual blood, sutures, or wires adjacent to
neurovascular bundle [7].
Nociceptive stimuli following trauma are transmitted to the central nervous
system via intercostal, thoracodorsal, long thoracic, vagus, or phrenic nerves.
Intercostal nerves usually carry somatic nociceptive stimuli to the dorsal
horn of the spinal cord by both fast-conducting, myelinated A delta and
slower, unmyelinated C-fibers [8].
Thoracodorsal and long thoracic nerves which arise from C5–C7 roots carry
nociceptive stimuli due to injury of latissimus dorsi and serratus anterior
muscles [9].
Surgical manipulation of the pleura/pericardium, diaphragm, or bronchi can
also result in a visceral stimuli transmitted by vagus and phrenic nerves.
Diaphragmatic irritation results in phrenic nerve stimulation that is usually
referred to ipsilateral shoulder pain (also known as postthoracotomy
shoulder pain, PTSP) [10]. Musculoskeletal components due to distraction
of posterior thoracic ligaments and brachial plexus stretching [11] also
contribute to PTSP development.
Chronic postthoracotomy pain syndrome (CPTP) is defined as “pain that
recurs or persists along a thoracotomy scar at least 2 months following the
surgical procedure” [4] and is thought to have neuropathic, myofascial, and
visceral components. CPTP is strongly related with acute postoperative pain
[12]. Other risk factors identified for CPTP besides acute neuropathic pain
are female gender, radiation therapy, presence of preoperative pain, and
extensive surgical trauma including pleurectomy.
Surgical technique plays an important role in both acute and chronic pain.
Thoracotomy for open lung resection usually involves a posterolateral incision
below the scapula tip (mostly at fifth intercostal space) and dissection of
latissimus dorsi and serratus anterior muscles [13]. Limiting incision size,
appropriate closing of the muscles, or avoiding splitting the latissimus dorsi can
decrease surgical trauma. In recent years, surgery is modified to completely or
partially preserve muscles (also called muscle-sparing thoracotomy), though
their effectiveness in reducing postoperative pain is controversial [14–16].
Anterolateral incision in which surgical exposure may be limited causes less pain
than posterolateral approach [17]. Acute pain due to classical techniques is more
severe than thoracoscopic procedures (i.e., video-assisted thoracoscopic surgery
or VATS). However, chronic pain can still be encountered in VATS (albeit at a
lower incidence) [18, 19] possibly due to trocar insertion trauma [20].
17.3 Consequences of Untreated Pain

Main clinical consequence of inadequate pain relief in thoracotomy patients is
altered pulmonary mechanics. Postoperative pulmonary dysfunction in
thoracotomy patients is a common result of a combination of multiple factors
such as preexisting lung disease, loss of parenchyma due to surgery, positioning,
single-lung ventilation, and pain [21]. Surgery is known to decrease vital
capacity as far as 15 % in lobectomy and 35–40 % in pneumonectomy [22].
Furthermore, general anesthesia itself may cause a functional residual capacity
(FRC) reduction up to 20 % [23], and this is increased in lateral position [24].
Lastly, the patient needs to breathe to avoid postoperative deeply pulmonary
complications. Thoracotomy patients often avoid deep breathing as it causes
further stretching of incision, and instead “splinting,” i.e., expiratory muscle
contraction, is observed. Thus, uncontrolled postoperative pain results in
decreased lung compliance, reduced functional residual capacity,
ventilation/perfusion mismatch, splinting, atelectasis, hypoventilation, hypoxia,
and hypercarbia [25].
Acute pain can also cause an increase in sympathetic flow, heart rate,
preload, and postload resulting in increased myocardial oxygen consumption
which may be deleterious in a patient with ischemic heart disease. For endocrine
consequences, pain is associated with catecholamine, ACTH, aldosterone,
cortisol, ADH, angiotensin, and glucagon increase which produces a catabolic
state with hyperglycemia and free water retention. Other repercussions of
untreated acute pain can be listed as altered coagulation, fibrinolysis, cytokine
production, and gastrointestinal motility and CPTP.
17.4 Treatment of Pain

A wide variety of techniques and analgesics can each target different points in
acute pain transmission. In the past, most authors agreed that optimal strategy
should be preemptive and multimodal, and hence a preoperatively placed
thoracic epidural catheter should be a standard in all patients undergoing major
open thoracic surgical procedures as stated by Gottschalk et al. [20]. In less than
10 years, all three standards (preemptive, multimodal, and thoracic epidural) in
this review, though still relevant, became somehow controversial.
17.5 Multimodal Analgesia

Postthoracotomy pain has complex mechanisms involving both incisional
(nociceptive) pain due to the damage of myofascial structures and neuropathic
component in transition from acute to chronic pain. To expect one method of
analgesia to be omnipotent is to set oneself for failure. For example, as explained
above, PTSP accompanying thoracic procedures is caused by afferent impulses
conducted with phrenic nerves and can be treated with a phrenic nerve blockade
[26], but not with thoracic epidural or paravertebral analgesia. To cover all the
components and the whole pathway of thoracotomy pain, using systemic
application of opioids would require very high doses with side effects and/or
remain inadequate. Therefore, systemic use of opioids is not a first-choice
treatment and should be considered at most as a “rescue” analgesic of other
methods.
Combining strategies acting on different sites of central and peripheral
nervous system is attractive as side effects of high-dose opioids can be avoided
with better analgesia. A commonly used strategy is to combine local anesthetics
(regional analgesia or infiltration), opioids, and non-opioid analgesics with
regional anesthesia as mainstay of pain relief. This strategy theoretically may
also aid in decreasing humoral inflammatory factors in circulation and hence
decrease central sensitization. Role of multimodal analgesia in prevention of
transition from acute to chronic pain is yet unknown [5].
17.6 Preemptive Analgesia

“Preemptive analgesia” concept, i.e., providing analgesia to prevent the
establishment of central sensitization caused by incisional injury – before the
noxious stimulus – had been initially advocated by experimental studies.
However, the promising results of experimental studies could not be confirmed
by following clinical studies [27]. Probably, this controversy was due to an
incorrect definition of the concept. As a matter of fact, it is not rational to expect
that only a preoperative peri-incisional injection of lidocaine would cause a
change in postthoracotomy pain [28]. In a new definition, “preventive analgesia”
should prevent the establishment of central sensitization caused not only by
incisional but also by inflammatory injuries, covering the whole preoperative
and early postoperative periods [29]. This should lead to an equal effective
analgesia with lower doses of analgesics. In a prospective randomized trial
comparing the effects of preoperative- or postoperative-initiated thoracic
epidural anesthesia (TEA) versus intravenous opioids, it has been found that the
preoperative initiation of TEA was associated with a significant improvement in
both acute and chronic postthoracotomy pain [3]. A meta-analysis on timing of
analgesia for postthoracotomy pain also showed that preoperative thoracic
epidural analgesia is associated with a better control of acute pain [30].
17.7 Regional Analgesia

17.7.1 Thoracic Epidural Analgesia/Anesthesia
Thoracic epidural analgesia (TEA) has been traditionally regarded to be the gold
standard in the treatment of postthoracotomy pain [31, 32]. TEA provides better
analgesia, better quality of life [33, 34], and better preservation of FRC [34]
compared to parenteral opioids. TEA is associated with a significant decrease in
postoperative pulmonary complications such as pneumonia and atelectasis [35,
36]. There is also evidence that TEA may prevent chronic postthoracotomy pain
[3] and provide beneficial anti-ischemic [37] and anti-arrhythmic effects [38].
One should also be aware of possible complications of epidural analgesia
such as failure to place the catheter, hypotension due to bilateral sympathetic
blockade, urinary retention, nausea, and rarely nerve damage, hematoma,
infection, and accidental intrathecal or intravascular spread with resulting local
anesthetic toxicity [39]. Therefore successful implementation of TEA depends
on provider’s attitude and conduct as with any anesthetic procedure. The concept
is linked to several questions concerning:
17.7.1.1 How to Do It?

As thoracic epidural catheterization requires a manipulation above the conus
medullaris (usually at T3–T9 level), there is possibility of medulla spinalis
injury. This procedure, combined with the fact that thoracic epidural catheter is
considered to be technically more difficult than the lumbar one, should be
performed “awake” (or “lightly sedated”) to warn the anesthetist of any possible
neurological injury. Placement of thoracic epidural catheters in anesthetized
patients has resulted in serious neurological damage [40]. Another advantage of
placing epidural catheters prior to anesthesia would be testing of sensory block
extension.
Epidural catheter is often advised to place between T3–T6 levels via a
paramedian approach. There are two main reasons for such a recommendation:
one is the extreme upward angulation of the processus spinosus at the mid-
thoracic region, and the other is possible ligamentum flavum midline gaps in
cervical and thoracic regions. With the same rationale, it is also recommended to
use “hanging drop” technique instead of “loss of resistance.” However, the
authors’ experience is that the more common approach of “loss of resistance” via
the median approach is still appropriate (and easy to perform) especially in low
thoracic levels. Furthermore needle for skin local anesthetic infiltration can also
be used as a “relatively noninvasive” guide to locate optimum insertion angle.
The line connecting the inferior angles of the scapula is the landmark of T8;
however this landmark should also be checked by counting up from the iliac
crest specifically in obese patients [41]. Of note, the catheter and solution
delivered should target dermatomes where nociceptive input originates to
provide better analgesia with minimal side effects (right place, right drug, and
right dose). Considering that the catheter would be inserted some 2–4 cm within
the epidural space, the optimal level for best epidural drug spread can be
adjusted. After high-thoracic epidurals, spread occurs markedly more caudal
than cranial. Conversely, low-thoracic epidurals have more cranial spread, while
at the mid-thoracic level, there is a homogenous spread in both directions [42].
17.7.1.2 Should It Be Mid-thoracic, or Is Low Thoracic

or Lumbar Also Possible?
The “congruence” of the catheter and the incision appears to be crucial. Placing
a catheter that does not coincidence with incision can result in lower pain relief
[43] and possible early removal of the epidural catheter because of ineffective
analgesia. Moreover, the advantages associated with the attenuation of the stress
response because of sympathetic blockade have been shown to be effective only
with extensive blockade [44]. On the other hand, many anesthetists (especially
the ones working in low-volume centers for thoracotomies and hence less
experience with TEA) tend to prefer lumbar epidural analgesia (LEA). This
approach can be advocated with a less possibility of neurologic injury and may
be performed also after anesthesia induction. However the success of such
approach depends on the use of opioids, specifically hydrophilic opioid
morphine which tends to spread to thoracic regions [45, 46]. Similarly, single-
shot intrathecal morphine may provide adequate pain relief for 12–24 h [47] with
doses ranging from 15 to 20 μg/kg [48].
17.7.1.3 What and How Much to Inject?

A combination of local anesthetic and opioids has apparent benefits over the solo
use of both drugs. The combination makes it possible to decrease the doses of
both drugs, leading to a decreased frequency and intensity of unwarranted effects
(e.g., less pruritus because of opioids and less motor blockade because of local
anesthetics). Furthermore local anesthetics have been shown to facilitate the
entry of opioid from the epidural space into the cerebrospinal fluid [49]. The
only possible drawback of adding opioid is the possibility of a late onset of
respiratory depression, but this can be minimized by using appropriate doses of
appropriate opioids.
Regarding local anesthetics, bupivacaine, levobupivacaine, and ropivacaine
are popular choices in differing concentrations. Application of the same amount
(=dose) of the epidural cocktail in different concentrations/volumes mostly
depends on “individual” choices. Although a case can be made to avoid
“intense” analgesia (even “anesthesia”) in a limited region for high concentration
in low-volume solutions in the postoperative period, this has not shown
clinically [50]. Regarding the choice of the opioid, epidural lipophilic opioids
such as fentanyl or sufentanil prefer to stay in epidural fat and have low spinal
bioavailability resulting in rather “narrow” but rapid-onset analgesia, whereas
hydrophilic opioids such as morphine can reach cerebrospinal fluid in higher
ratio and can achieve a “wider” analgesia despite increased nausea/vomiting and
late onset of action. The optimal concentration of epidural fentanyl for
bupivacaine 0.1 % was found to be 5 μg/ml [51]. Our center also uses patient-
controlled epidural analgesia with bupivacaine 0.1 % and morphine 0.05–0.1
mg/mL solution successfully [52].
Several adjuvants have been studied regarding their effectiveness in TEA.
Among them, magnesium [53], ketamine [54], clonidine [55], dexmedetomidine
[56], and neostigmine [57] appear to be promising. They all are reported to be
associated with a reduction in postoperative analgesic requirement; the effects on
chronic pain are rather controversial. Unfortunately, almost all of these drugs are
to be used “off-label” via the epidural route; this is maybe the most important
reason why their use is limited to scientific trials.
17.7.1.4 When to Start?

As explained above, preoperative insertion and dosing of epidural catheter and
onset of analgesia prior to incision while continuing analgesics in the
postoperative 48–72 h can provide “preventive analgesia.” In our institution, a
loading dose of 10 mL of aforementioned epidural solution is applied before the
surgery, and a constant infusion rate of 7–10 mL/h is continued throughout the
surgery. However, one should be aware of possibility of hypotension at the start
of surgery and be ready to counter this either by decreasing the general
anesthetic levels with the depth of anesthesia monitoring or if necessary low
doses of vasopressors. Obviously, loading the patient with fluids should be
avoided in these cases, as long as the reason of hypotension is not hypovolemia.
Second concern to preoperative or intraoperative use of TEA is that it may lead
to pulmonary vasodilation. It can be assumed that the hypoxic pulmonary
vasoconstriction would be inhibited, with a consequent increase in pulmonary
shunt and decrease in oxygenation. Although there are some studies supporting
this assumption, the increase in shunt and decrease in oxygenation appear to be
statistically insignificant and clinically irrelevant with both isoflurane and
propofol [52]. During the postoperative period, PCEA protocol with no loading
dose, basal infusion of 5 mL/h, 3 mL bolus dose, and 30-min lockout period is
used in our institution. However, this regimen is also tailored in each patient
individually.
17.7.2 Paravertebral Block

Paravertebral block (PVB) with its fast-growing popularity is now considered as
a serious and in some cases an even more appropriate alternative of TEA [58].
Unnecessary bilateral sympathetic blockade resulting in hypotension and urinary
retention encountered in TEA can be avoided with PVB, and possibility of
neurological injury, hematoma, epidural abscess, accidental intrathecal injection,
and systemic local anesthetic injection, although theoretically possible, is lower
in PVB than TEA. Specific complications listed for PVB include ipsilateral
Horner syndrome and pneumothorax. As with TEA, infection at injection site,
severe coagulopathy, and deformities of the spine resulting in technical difficulty
to perform the block are the main limitations to the use of PVB. Furthermore,
PVB should not be performed in patients depending on intercostal muscles for
ventilation or in patients with ipsilateral diaphragmatic paresis.
In terms of outcomes, although its effect on preventing chronic
postthoracotomy pain is unknown, recent reviews have stated that PVB is a safe
and superior alternative to TEA for dynamic analgesia [59] and has comparable
efficacy to TEA in static analgesia [60]. PVB is also successful in preserving
pulmonary function and preventing complications such as failure of technique,
hypotension, need for vasopressors, urinary retention, nausea and vomiting, need
for ventilator support, need for reoperation, arrhythmia, anastomosis leak, and
sepsis [5, 11]. Of note, most studies reporting better or comparable analgesia
with TEA have been placed by the surgeon under direct vision. Also one should
keep in mind that its efficacy would be limited following single-shot injection.
Furthermore, according to a systematic review and metaregression study by
Kotze et al., the effectiveness of PVB is increased with continuous infusion
techniques when compared to intermittent boli [61]. This study also reported that
higher doses of bupivacaine provided better analgesia when compared to lower
doses. When using high doses, albeit infrequently, local anesthetic toxicity is
possible especially if the pleural integrity is not preserved as absorption of the
local anesthetic is faster from the pleural space compared to the paravertebral
space [62].
The anatomy of the thoracic paravertebral space plays an important role in
the application of PVB. This is a wedge-shaped space bounded medially by the
bodies of the vertebrae, intervertebral discs, and intervertebral foramina,
anterolaterally by the parietal pleura and the innermost intercostal membrane,
and posteriorly by the transverse processes of the thoracic vertebrae, heads of the
ribs, and the superior costotransverse ligament.
In the classical technique, needle is inserted 25 mm lateral to the spinous
processes of the targeted vertebrae and directed posteroanterior till pars
intervertebralis, articular column, or transverse process is encountered. Once the
bone is met, needle is advanced in an inferior (caudal) and lateral direction while
testing for a change in resistance. Change in resistance indicates penetration of
the costotransverse ligament and identification of paravertebral space. We will
not explain the technique of PVB in details, but one important point is that there
should be a feeling of “change in resistance” as the needle is advanced caudally
beyond the costotransverse ligament and needle insertion depth should be
predefined (i.e., no more than 10–15 mm) [63]. This means a “click” and a “loss
of resistance” similar to the ones in TEA should be avoided, for they may
indicate a pleural puncture. Another important point to remember is cranial
advancement can increase the risk of pleural puncture, whereas medial
angulation can cause epidural, intrathecal, or spinal injection.
Although technically easy, an unacceptable high rate of misplacement is
shown with classical landmark technique radiologically [64]. The advance of
ultrasound technology has enabled us to visualize the transverse process,
costotransverse ligament, and paravertebral space and pleura. The use of
ultrasound, albeit time costly, can reduce misplacement and/or complications
either with assistance as distance to paravertebral or pleural space can be
measured prior to block or with direct needle visualization and guidance in real
time during the block [65, 66]. Furthermore, anterior displacement of parietal
pleura with injection of local anesthetic can be observed.
Interestingly, in magnetic resonance imaging studies, a discrepancy can be
observed between spread of local anesthetic and somatic analgesia (i.e., although
the injected local anesthetic only encompassed four vertebral levels, sensory
block levels were more extensive and showed high variability) which is
explained by some via a possible secondary epidural spread [67].
17.7.3 Intercostal and Interpleural Block

For intercostal block, each intercostal nerve is targeted at inferior rib margin in
intercostal space. In these blocks, local anesthetic spread is mostly distal, and
proximal spread is relatively limited unlike PVB requiring multiple injections
and high amount of local anesthetics with possible systemic toxicity side effects
for effective analgesia. However, these blocks provide fast, easy, and valuable
alternative in patients when TEA and PVB cannot be used. Although intercostal
nerve blocks have been shown to be effective especially in multiple injections
and continuous infusions in a meta-analysis [31], this has not been the case for
single-shot block [68]. Yet, there is recent interest in these blocks with the use of
long-acting bupivacaine liposome [69].
Interpleural analgesia targets the spread of local anesthetic from interpleural
space in a retrograde manner to intercostal and paravertebral space. However,
this technique is not recommended due to possibility of air entrapment
(pneumothorax) during needle pass through the pleura, large doses of local
anesthetic requirement (systemic toxicity), and loss of drug via chest tubes [31].
17.7.4 Continuous Wound Catheter Analgesia
Continuous wound analgesia via ON-Q infiltration catheter had been advocated
as an easy and cheaper route to administer local anesthetics compared to TEA
while providing efficient analgesia for open thoracotomies [70]. However,
analgesic efficacy was not confirmed in a study comparing wound analgesia with
TEA and PVB [71]. Recently, a study comparing wound catheter analgesia with
placebo has demonstrated better analgesia, accelerated recovery of respiratory
dynamics, and suppressed postoperative inflammation markers in wound
analgesia group [72].
17.7.5 Other Techniques

Cryoanalgesia which involves neurolysis by freezing intercostal nerves is
nowadays an abandoned technique as its use is associated with chronic
postthoracotomy pain [73]. Neuromodulation via transcutaneous electrical nerve
stimulation (TENS) is a frequently underutilized technique that can complement
regional or systemic analgesia and has been shown to be effective together with
pharmacological analgesia when compared to TENS alone [11, 74].
17.8 Systemic Analgesia

17.8.1 Opioids
Intrathecal and epidural routes for opioid administration have been discussed
above. Parenteral opioid administration is not preferred as a first choice in
thoracotomy patients due to a high rate of unwarranted/warranted effects such as
nausea and vomiting, constipation, altered mental status, and respiratory
depression. However, in patients where regional blocks are not applicable, they
can be used.
17.8.2 Acetaminophen and Nonsteroidal Anti-

inflammatory Drugs (NSAID)
Acetaminophen, a weak prostaglandin and cyclooxygenase (COX)-II and COX-
III inhibitor, has been shown to decrease ipsilateral shoulder pain in thoracotomy
patients when given preemptively [75]. This drug can be administered via oral,
rectal, and intravenous route and is a relatively safe drug in doses less than 4000
mg/day in adult patients. However, one should be cautious in higher doses or in
patients with hepatic diseases. Classical NSAIDs such as ketorolac can decrease
opioid requirements but are associated with gastrointestinal, renal, and
cardiovascular side effects and may impair coagulation. More studies are needed
to elucidate if new formulations of old drugs enabling parenteral use (such has
ibuprofen) can achieve similar or yet better analgesia. COX-II selective
inhibitors (such as parecoxib, celecoxib, nimesulide) can also reduce opioid
consumption in an equally effective manner but do not impair coagulation.
Several studies have reported successful use of NSAIDs and COX-II inhibitors
for thoracotomy patients [76–78]. These drugs may also be important in
suppressing postoperative inflammatory response [79], but studies are needed to
investigate their effects on transition from acute to chronic pain.
17.8.3 Ketamine
Ketamine, a noncompetitive antagonist of N-methyl-D-aspartate (NMDA)
receptor, has unique analgesic effects in patients with opioid tolerance, pain with
neuropathic component, and acute hyperalgesia. Ketamine may be associated
with an increase in neuropsychiatric disturbances but may decrease side effects
of opioids such as nausea and vomiting or respiratory depression. Analgesic-
sparing effects of intravenous subanesthetic doses of ketamine have been
demonstrated for parenteral and paravertebral analgesia [78, 80], but not for
TEA [81]. Similarly, ketamine was not shown to be effective in preventing CPTP
[11].
17.8.4 Gabapentin and Pregabalin

Gabapentinoids, presynaptic calcium channel agonists, are effective in treating
neuropathic pain. Common side effects of these drugs are visual disturbances,
drowsiness, and vertigo which at times cannot be tolerated. Gabapentin has not
been effective in preventing acute pain [82], and evidence on chronic
postthoracotomy pain is conflicting [83, 84]. Interestingly, pregabalin has been
shown to be effective in acute pain, CPTP, and PTSP [85–88].
17.8.5 Other Agents

Postoperative intravenous infusion of selective alpha-2-adrenergic receptor
agonist dexmedetomidine has been shown to decrease opioid requirements [89,
90].
Conclusion
The effective treatment of postthoracotomy pain is one of the most important
tools of thoracic anesthesia, playing an essential role in the outcome of thoracic
surgery. However, neither has the exact pathogenesis been explained nor has the
“best” analgesic method been defined. Proper patient preparation followed by
comprehensive teamwork to apply the analgesic regimen, to monitor its effects,
and to treat its side effects and complications should not be underestimated.
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DOI 10.1007/978-3-319-19908-5_18
18. Rehabilitation for Thoracic Surgical

Patients: Why, When, and How
Grégoire Blaudszun1, Frédéric Triponez2, Pierre-
Olivier Bridevaux3 and Marc Joseph Licker1
(1) Department of Anaesthesiology, Pharmacology, and Intensive Care, Geneva
(2) Service of Thoracic and Endocrine Surgery, Geneva University Hospitals,
Geneva, Switzerland
(3) Division of Pulmonary Medicine, Geneva University Hospitals, Geneva,,
Switzerland

Marc Joseph Licker
Email: Marc-Joseph.Licker@hcuge.ch
18.1 Physical Fitness: A Marker of Health

A wealth of studies has provided convincing evidence of the remarkable ability
of aerobic fitness to assess general health status and to predict all-cause mortality
in numerous adult populations. According to the World Health Organization
(WHO), physical inactivity is highly prevalent in both Western and emerging
countries (31 % in men and 34 % in women) and has become the fourth leading
risk factor for global mortality – just behind hypertension, tobacco-related
illnesses, and diabetes mellitus. Approximately 3.2 million deaths are
attributable each year to poor physical activity (http://whqlibdoc.who.int/
publications/2010/9789241599979_eng.pdf).
Likewise, assessing aerobic fitness is helpful in preoperative risk
stratification as poor physical performance is considered a valuable predictor of
mortality and morbidity as well as prolonged hospital stay following major
surgical procedures.
Using self-report questionnaires such as the Duke Activity Status Index or
simple motion detectors (accelerometer, pedometer), physical fitness can be
qualitatively rated in metabolic equivalents of task (METs), one MET being
equivalent to the amount of energy expanded or oxygen consumed (VO2) at rest
(0.8–1 kcal.kg-1.hour-1, resting VO2 2.5–3.5 ml.kg-1.min-1). Physical fitness
level is inversely related to mortality after adjustment for the presence of
cardiopulmonary disease, socioeconomic factors, and age, 1-year mortality
increasing by 13 % for every 1 MET decrement in exercise capacity [1].
Aerobic physical fitness as assessed quantitatively by the maximal or peak
oxygen consumption (VO2peak, VO2max) reflects the integrative functioning of
the pulmonary and circulatory systems, blood oxygen-carrying content
(hemoglobin), and skeletal muscle mechanical performances. Oxygen transport
from the environment to the skeletal muscle mitochondria entails a series of
convective and diffusive steps, the so-called oxygen cascade that represents key
processes essential for oxidative metabolism implicated in cellular growth,
internal enzymatic processes, and mechanical work (Fig. 18.1). As genetics
accounts for only 20–30 % of VO2peak values, morphometric characteristics,
lifestyle, and concomitant diseases are the main contributory factors in human
aerobic capacity. Compared with men, VO2peak is approximately 15–25 % lower
in women and decreases on average by 5–15 % per decade, the decline being
sharper among sedentary persons and after the age of 60.
Fig. 18.1 Oxygen cascade
Considerable evidence suggests that exercise training programs may alleviate

symptoms and improve long-term outcome in various diseases such as chronic
obstructive pulmonary disease (COPD), diabetes, arterial hypertension, heart
failure (HF), coronary artery disease, cancer, and neuropsychiatric disorders.
Over the last 15 years, some clinicians have hypothesized that implementation of
exercise training programs prior to and/or following surgery had the potential to
“recondition” the patient by increasing aerobic fitness and thereby minimizing
perioperative risk of major organ dysfunction while enhancing functional
recovery soon after surgery.
In this chapter, we will review the current knowledge regarding
physiological impairment observed in thoracic surgical patients, the mechanisms
underlying endurance and strength exercise-induced improvement in physical
fitness, and the efficacy of exercise training program when prescribed prior to
and/or after surgery.
18.2 Physical Fitness in Thoracic Surgical Candidates

18.2.1 Assessment of Fitness Before Surgery
Cardiopulmonary exercise testing (CPET) on a cycloergometer or a treadmill
represents the gold standard to assess patient’s physical fitness and the
effectiveness of physical training interventions. Besides VO2peak (highest value
attained during CPET) and VO2max (plateau level of VO2 achieved beyond
which no increase in effort can raise it further), other parameters such as peak
workload or peak power (Wmax), peak heart rate (peakHR), O2 pulse
(VO2/HR), ventilator equivalent for CO2 (ratio of minute ventilation to the
production of carbon dioxide, VE/VCO2), anaerobic threshold (AT), and
respiratory gas exchange ratio (VCO2/VO2) all characterize the patient’s aerobic
capacity. Overall, the predicted VO2max of any individual takes into account age,
gender, height, and lean body mass. Alternate testing modalities have also been
developed and validated to provide physiological surrogates of patient’s physical
fitness as derived from stair climbing (speed of ascent, number of stairs) and the
shuttle test or the 6-min walk test (6MWT, distance) (Table 18.1). In elderly and
“frail” patients, simple tests of active mobilization such as the gait speed test
(time needed to walk 5 m), maximal handgrip strength test (dynamometer),
recording of all movement throughout the day (pedometer, accelerometer), the
mini-mental test, and subjective performance scoring status (e.g., Karnofsky
Performance Status) all complement valuable information on patient physical
autonomy and bear important prognostic significance.
Table 18.1 Cardiorespiratory fitness testing modalities
Cardiopulmonary Stair climbing or other Shuttle or 6- Age-predicted HR test
exercise testing CPET physical stress tests min walk test
Maximal Submaximal
Principle Direct measurements Estimated VO2max from Distance (m) Workload achieved at
of VO2, VCO2, HR, highest workload, HR 70–85 % PredHR
BP, and airflow achieved
Equipment Cycle Stair climbinga (6 floors) 30-m corridor Cycle
ergometer/treadmill or cycle monitor HR, ergometer/treadmill
Expired–inspired gas ergometer/treadmill SpO2, stop monitor HR, SpO2, BP
HR (SpO2, BP) (SpO2,BP, ECG) watch (ECG), stop watch
Duration 8–12 min 5–20 min 4–6 min 5–20 min
Operative risk
Low VO2 max >20 >22 m altitude or 6 floors >600 m
ml/kg/min or 15 m/min
Moderate VO2 max 15–20 8–20 m alt. or 3–5 floors
ml/kg/min
High VO2 max 10–15 3–7 m alt. or 1–2 floors 400 m
ml/kg/min
Very High VO2 max < 10 <2.4 m alt. or 1 floor
ml/kg/min
BP blood pressure, ECG electrocardiogram, HR heart rate, SpO2 pulsed oxygen

saturation, VO2max maximal oxygen consumption
aStair climbing test assumes reasonable speed of ascent
Guidelines issued from the American College of Chest Physicians (ACCP),

from the British Thoracic Society (BTS), and jointly from the European Society
of Thoracic Surgeons and the European Respiratory Society (ESTS/ERS) all
recommend performing CPET whenever the diffusion capacity for carbon
monoxide (DLCO) and/or forced expiratory volume in 1 s (FEV1) are below 80
% of predicted values [2–4]. The scientific rationale to perform CPET is to
identify “unfit” subjects – those with low VO2peak – who might not be able to
sustain the postoperative physiological impairments and the increased metabolic
burden consequent to the surgical-induced neuroendocrine and inflammatory
responses. Cutoff values of 15–16 ml.kg-1.min-1 VO2max (four METs) and 10–
12 ml.kg-1.min-1 anaerobic threshold (three METs) have been shown to be
helpful in discriminating patients at low–moderate risk and those at high (or very
high) risk of major postoperative complications.
Importantly, patients with lung cancer awaiting surgery and particularly
those receiving chemotherapeutic agents present VO2max on average 25–30 %
lower than age- and gender-matched individuals (sedentary, active, or trained)
(Fig. 18.2).
Fig. 18.2 Aerobic capacity assessed in healthy men and women (sedentary, active, and trained) and in
patients with lung cancer receiving or not neoadjuvant chemotherapy
18.2.2 Causes of Poor Physical Fitness

Among thoracic surgical patients, the loss of muscular mass and aerobic physical
fitness is often multifactorial as a result of aging, physical inactivity, tobacco-
related illnesses, tumor burden, and chemotherapy, with no single organ or step
of the oxygen cascade being identified as solely responsible.
Based on CPET, poor aerobic physical fitness is primarily linked to
respiratory limitations (ventilator and gas exchange capacity), cardiovascular
limitations (cardiac and vascular components, hemoglobin level), skeletal
muscle limitations (muscular deconditioning, joint disorders, or neurological
deficits), or a combination of these factors. The age-related decline in VO2max is
largely attributed to impaired peripheral oxygen utilization coupled to the loss of
lean body mass and decreased HR reserve (downregulation of β-adrenergic
receptor and cardiac autonomic imbalance) that limits the exercise-induced
increase in cardiac output. Likewise, a sedentary lifestyle, malnutrition, and
prolonged immobilization have all been associated with low VO2max owing to
lower heart rate response, loss of skeletal muscle mass, and impaired
mitochondrial oxidative capacity.
18.2.3 Stress- and Inactivity-Induced Muscle Wasting

After surgery, afferent nerve signals from the injured tissues and pro-
inflammatory cytokines released from activated leukocytes, fibroblasts, and
endothelial cells all activate the sympathetic nervous system and the
hypothalamic–pituitary axis. This so-called surgical stress-induced
neuroendocrine and inflammatory response is proportional to the extent of tissue
trauma. Concomitant to the peak release of inflammatory mediators and counter-
regulatory hormones (cortisol, catecholamines, and glucagon), basal VO2 and
VCO2 have been shown to increase by 10–25 % within the first 2 days after
thoracic surgery, peaking at 30–45 % in patients with pneumonia [5, 6]. This
hypermetabolic state reflects increased synthesis of acute phase proteins in the
liver and enhanced tissue repair activity involving leukocytes, fibroblasts, and
mesenchymal cells. The high levels of counter-regulatory hormones lead to a
decrease in glucose cellular uptake/utilization (insulin resistance) and promote
the breakdown of skeletal and visceral proteins into amino acids, as well as
degradation of fat into glycerol and free fatty acids. Both amino acids and
glycerol serve as substrates for hepatic neoglucogenesis and protein synthesis,
while energy needs are predominantly met by free fatty acids in most tissues,
except a few obligate glucose users (e.g., leukocytes, red blood cells, neurons).
Following major surgery, urinary nitrogen excretion increases to 40–100 g
per day reflecting early muscle wasting (loss of 2–4 kg skeletal muscles) that
takes several weeks for complete recovery [7]. The ensuing muscle weakness
and fatigability when completing minor tasks impede early mobilization and
return to functional autonomy. Frail subjects with sarcopenia and altered
capacity to utilize nutrients are prone to experience postoperative multiorgan
dysfunction resulting in admission to intensive care units (ICU), prolonged
hospital stay, and discharge in institutional care facilities.
Besides the neuroendocrine and inflammatory components, physical
inactivity associated with the intraoperative and postoperative period causes
maladaptive changes in organ components of oxygen transport. Muscular disuse
associated with short immobilization periods (5–10 days) has been shown to
result in loss of muscle mass and strength due to an accelerated protein
breakdown and in lower VO2max (−10–20 %) owing to reduced cardiac output
and reduced red blood cell mass [8]. Interestingly, among all skeletal muscles,
the diaphragm is most prone to inactivity-induced proteolysis leading to the so-
called ventilation-induced diaphragmatic dysfunction. Unlike nonrespiratory
muscles in the limbs or thoracoabdominal wall, the functioning and morphology
of the diaphragm have been shown to be sensitive to ventilation-induced muscle
loading conditions. In brain-dead patients, Levine et al. reported severe
diaphragm muscle fiber atrophy after 18–69 h of mechanical ventilation,
whereas pectoralis muscle fibers were entirely preserved [9]. An average 30%
loss of the force-generating capacity of the diaphragm has been observed
following thoracic surgery with short mechanical ventilation periods (less than 2
h), whereas the contractile performance of latissimus dorsi muscle was preserved
[10].
18.3 Exercise-Induced Muscular and Cardiopulmonary

Function
Compared with pharmacological interventions, exercise training is currently
recognized as one of the most efficient interventions to improve physical and
psychological health in patients with cardiovascular, pulmonary, and rheumatic
diseases as well as with cancer, obesity, or mental disorders.
18.3.1 Type of Exercise

Physical training programs encompass resistance or strength-type exercises and
endurance or aerobic-type exercises. Increasing muscular mass is usually
achieved by “resistive work” or static (isometric) contraction without any change
in muscle length. In contrast, dynamic (isotonic) muscle actions entail concentric
and eccentric contractions leading to muscle shortening and lengthening,
respectively.
18.3.2 Mechanism of Exercise-Induced Improvement in

Physical Fitness (Fig. 18.3)
Fig. 18.3 Mechanisms of exercise-induced changes in muscle fiber phenotype
In “frail” sarcopenic subjects, resistance exercises (isometric contractions)

are particularly effective in (re)building up muscle mass (hypertrophic changes
dominates hyperplasia) with significant improvement in strength and joint
mobility. In contrast, aerobic exercises lead to a minor increase in muscle
mass/strength, but their beneficial health benefits are attributed to attenuation of
systemic inflammation, enhanced angiogenesis, and phenotypical changes of
cardiac and skeletal myocytes from type IIb into type IIa fibers with increased
oxidative capacity (Fig. 18.3). The mechanisms underlying the aerobic exercise-
induced increase in VO2max are multifactorial involving partial reversal of
endothelial dysfunction and adrenergic receptor responsiveness, higher capillary
density, restoration of insulin sensitivity, and enhanced mitochondrial
performances owing to tighter coupling between beta-oxidation and the
tricarboxylic acid cycle. The enhanced cardiac output and facilitated tissue
oxygen diffusion coupled with greater extraction of oxygen by the working
muscle all contribute to increase in aerobic capacity after short training periods
(Table 18.2).
Table 18.2 Mechanisms of exercise-induced improvement in oxygen transport components
Oxygen transport component Long term Short term Comment
(≥4 weeks) (<4 weeks)
Pulmonary Respiratory muscles (breathing = = Respiratory muscle training is
exercise) associated with reduced dyspnea
Diffusion capacity = =
Airway obstruction, airflow = = Improved by bronchodilators
trapping
Pulmonary vascular (remodeling) = =
Cardiac Systolic ventricular function ↗or = ?
(contractility)
Diastolic ventricular function ↗or = ?
(relaxation)
Peak stroke volume ↗↗ (↗)
Peak heart rate ↗↗ ↗
Ventilatory equivalents at ↙ ?
ventilatory threshold
Cardiac Output ↗↗↗ (♂ > ↗ (♂ > ♀)
♀)
Tolerance to myocardial ischemia ↗ ↗
Vascular Endothelial function (NO release) ↗ ↗
Arterial stiffness ↙ ?
Anti-inflammatory expression ↗ ?
Blood Hemoglobin concentration ↗ =
All Ventilatory (anaerobic) threshold ↗ ?
Skeletal Arteriovenous oxygen difference = elderly ♂
muscle ↗elderly ♀
Capillary density ↗ ?
Enzymes for oxidative ↗↗ ↗
phosphorylation
Mitochondrial density ↗↗ ↗
Myoglobin concentration ↗ ?
Fiber transition to fatigue Yes ?
resistant phenotype (type I to type
IIA)
Muscle mass ↗ (↗)

↗ enhancement, ↙ decrement, = no change
18.3.2.1 Experimental Data

In several animal models, repeated bouts of intense muscular activity (equivalent
to high-intensity interval training [HIIT]) to achieve 80–90 % HRmax or VO2max
have demonstrated cardioprotective effects quite similar to ischemic
preconditioning. Protective cellular processes in the heart are mediated by
sarcolemmal and mitochondrial ATP-sensitive potassium channels, generation of
antioxidant molecules (superoxide dismutase, catalase), overexpression of heat
shock protein (HSP70, HSP27), and upregulation of autophagic responses (Fig.
18.4). Exercise-induced cardiac mitochondrial adaptations have been shown to
result in decreased reactive oxygen species production, increasing the heart’s
ability to tolerate high calcium levels and to sustain subsequent acute ischemic
events.
Fig. 18.4 Organ-protective mechanisms induced by aerobic high-intensity training. EPC endothelial
progenitor cells; NO nitric oxide; SCDF stromal cell-derived factor; COX-2 cyclooxygenase type 2; PKC
protein kinase C; AMPK adenosine monophosphate kinase; ROS reactive oxygen species; AMP, ADP, and
ATP adenosine mono-, di-, and triphosphate; mPTP mitochondrial permeability transition pore; mito and
sarco KATP mitochondrial and sarcolemmal potassium ATP channel
Regarding the risk of ventilation-induced diaphragmatic dysfunction,

Smuder et al. elegantly demonstrated that endurance training (10 days, 60-min
treadmill at 70 % VO2max) increased both antioxidant and HSP72 capacity while
minimizing oxidative damage, protease activation, diaphragm myofiber atrophy,
and contractile dysfunction induced by 12-h mechanical ventilation [11]. Similar
short-lasting training programs in rats (running in a wheel) have been shown to
protect against lung ischemia–reperfusion injuries and preserve alveolar–
capillary permeability by limiting pro-inflammatory mediators (TNF-alpha and
IL-1) and oxidative stress (superoxide dismutase activity) [12].
18.3.2.2 Clinical Data

Even short-term aerobic or endurance exercise programs (1–3 weeks) have been
shown to improve physical fitness reflected by increases in VO2max, maximal
workload, ventilatory aerobic threshold, anaerobic threshold coupled with faster
heart rate recovery (expressing sympatho-vagal balance), and lesser fatigue.
Perceived dyspnea is often alleviated although airflow limitation and diffusion
capacity remain unchanged. The increased VO2max is mainly related to increase
in peak stroke volume and peak HR in elderly man, whereas widening in peak
arteriovenous oxygen difference predominates in elderly woman, suggesting
gender differences in cardiovascular and skeletal muscle responses to exercise
training.
In the context of surgery, physical training modalities need to be tailored to
achieve favorable results within a short time frame (2–4 weeks). Compared with
continuous low-intensity training, 8 weeks of HIIT in sedentary individuals have
been shown to provide greater improvements in VO2max (+22 % vs 15 %) and
left ventricular mass (6 % vs 1 %) with faster post-exercise recovery of HR
consistent with enhanced vagal neural tone [13]. Similar findings have been
reported in patients with CHF after 4 weeks of supervised HIIT (average 7
h/week): the increased VO2max (+26 %) and improved left ventricular function
were associated with a reduced expression of MuRF-1 levels in skeletal muscles,
reflecting lower catabolic activation of the ubiquitin–proteasome system [14,
15]. Reversal of endothelial dysfunction and improvement of oxygen delivery in
the skeletal muscles have been related to the mobilization of bone marrow-
derived endothelial progenitor cells (EPCs), nitric oxide (NO), and stromal cell-
derived factor (SCDF) following short training period among healthy sedentary
subjects, in frail elderly, and in patients with cardiovascular diseases [16]. This
angiogenic response can be further amplified by performing intermittent
physical training in a hypoxic environment [17].
18.4 Exercise Training in Patients Undergoing Thoracic
Surgery: Prohabilitation and Rehabilitation
Currently, only 10–20 % of patients diagnosed with lung cancer are eligible for
curative surgical resection. Reasons to dismiss surgical treatment are not only
related to advanced disease stage (TNM stage IIIB, IV) or histological type
(small cell carcinoma) but also to comorbidities and poor functional capacity
that are amenable to appropriate therapeutic strategies. According to the
ESTS/ERS guidelines, patients with VO2max < 10 ml/kg/ml are declared unfit for
major surgical resection, and those with VO2max < 14–16 ml/kg/min are
considered at high risk of postoperative cardiopulmonary complications [2].
Physical interventions aimed at enhancing patient’s functional capacity
before surgery and to improve the tolerance to postoperative surgical stress have
been lumped under the concept of “prohabilitation” in contrast to
“rehabilitation” that is related to physical therapy prescribed after surgery to
speed up functional recovery.
The preoperative period represents a window of “therapeutic opportunity”;
patients are in better physical condition than in the early postoperative period
and more receptive to adopt a “healthy behavior” (tobacco and alcohol cessation,
enhanced mobilization, better diet). Whether patient’s poor physical fitness is
“intrinsic” or “reversible” by implementing structured exercise programs
associated (or not) with nutritional and psychological support remains
questionable.
A growing interest is now focusing on non-pharmacological interventions
such as physical exercise, smoking cessation, nutritional supplementation, and
psychological support aimed to optimize patient physiological condition before
and/or shortly after thoracic, cardiac, orthopedic, and abdominal procedures.
Since 2000, 13 meta-analyses and systematic reviews encompassing more than
50 studies have been published in the field of preoperative preparation, aerobic
exercise training, and postoperative rehabilitation [18–30]. Short-term exercise
training by improving aerobic fitness could potentially increase the number of
candidates for curative therapy. The interval of time from diagnosis to curative
cancer surgery should not exceed 4 weeks and would be sufficient to partly
reverse the poor functional capacity by improving patient’s physiological
reserves.
In abdominal and cardiac surgery, a systematic review including 12 RCTs
reported shorter length of hospital stay and fewer postoperative pulmonary
complications among patients enrolled in various forms of preoperative exercise
training programs [30]. A preoperative inspiratory muscle training program
(incentive spirometry; education in active cycle of breathing and forced
expiration techniques) was shown to prevent postoperative pneumonia and
reduce length of hospital stay [31]. In contrast, another systematic review of 8
RCTs failed to demonstrate exercise-induced physiological and clinical benefits
in patients undergoing cardiac, abdominal, or orthopedic surgery [22]. Failure to
achieve favorable effects could be attributed to poor adhesion and low
attendance to the program as well as performance of low-intensity aerobic
exercise program. More recently, among patients scheduled for colorectal
surgery, Gillis et al. demonstrated the superiority of a trimodal reconditioning
program (exercise, diet, and anti-stress therapy) conducted preoperatively
instead of postoperatively, as evidenced by better recovery of walking capacity 8
weeks after surgery; however, the length of hospital stay and the incidence of
perioperative complications were similar regardless of the timing of the
optimization strategy [32].
Regarding thoracic surgery, a literature search from 1990 to 2015 yielded 14
cohort studies (N = 365: 49 prohabilitation, 316 rehabilitation) [33–46] and 8
RCTs (N = 381: 196 prohabilitation, 185 rehabilitation) [47–54] focusing on
different exercise training protocols and reporting objective measures of physical
fitness (walking capacity, VO2max, peak work rate), pulmonary function, blood gas
exchange, and/or clinical outcome along with health-related quality of life
parameters (HRQL).
Altogether, these studies support the safety and feasibility of implementing
physical training programs within a limited time frame before surgery (11 days
to 4 weeks) that can eventually be continued postoperatively. Minor adverse
effects such as transient hypotension, low back pain, or exacerbation of shoulder
arthritis have been reported anecdotally. The variable eligibility rate (from 20 to
85 %) mainly depended on the existing physiological status and the
inclusion/exclusion criteria, some investigators excluding patients with
cardiovascular diseases, those with joint or neurological disabilities, and those
with neuropsychological disorders. Among patients enrolled in the training
program, the completion/retention rate was fair (60–100 %) along with variable
attendance to most planned sessions (from 40 to 125 %), except in patients
treated with adjuvant chemotherapy (43 % attendance).
Six of eight RCTs reported some improvement in at least one surrogate
marker of physical fitness after prohabilitation intervention. In four of six studies
using CPET, mean VO2max or mean VO2peak improved by 1.7–6.3 ml/kg/min
(approximately +10–20 % of predicted VO2max/peak) along with significant
increase in peak workload (+25–35 % power). Consistent with these findings,
nine of ten studies using the 6MWT reported a significant increase in walking
distance (+28 m to 377 m) and reduced fatigability after prohabilitation.
Unchanged walking distance at the 6MWT (one study) could be explained by
therapy focusing only on muscle strength training. Regarding health quality of
life (QOL), few favorable outcomes were observed that might be related to the
possible ceiling effect or the use of nonvalidated questionnaires. Regarding
clinical outcomes, despite consistent reports of improved exercise capacity, a
lower rate of postoperative complications was observed in only one small RCT
(N = 24), and a shorter hospital stay was reported in 3 RCTs in the
prohabilitation group compared with the control group.
Not surprisingly, insignificant changes in airflow limitation (forced vital
capacity and forced FEV1) and in gas exchange (diffusion capacity to carbon
monoxide [DLCO]) were reported after short-term prohabilitation intervention.
In a small prospective study (N = 22 COPD patients), Sekine et al. reported that
intensive chest physiotherapy (incentive spirometry, breathing exercise)
combined with walking (>5’000 steps/day), which started on average 2 weeks
preoperatively and continued postoperatively, resulted in a lesser fall in FEV1,
lesser requirement for oxygen therapy, and shorter length of hospital stay after
lobectomy [44].
The rather low quality of these studies (selection biases, noncontrolled
studies) and lack of relevant clinical endpoints (major postoperative
complications) preclude any conclusions regarding the benefits of the physical
interventions in the perioperative period.
The overall methodological quality was poor to moderate with an overall
high to unclear risk of bias. Few RCTs have been conducted so far and include
small numbers of patients. Hence, the generalizability of these preliminary
positive findings is further limited due to considerable heterogeneity in
therapeutic protocols and outcome measurement across studies, notwithstanding
the exclusion of patients with significant comorbid diseases, a population that
has the potential to benefit most from pre- and postoperative physical training.
Conclusion
The risk of developing major postoperative complications is partially related to
“modifiable” factors, aerobic fitness, smoking habits, alcohol consumption, and
poor nutrition. Low VO2max or poor exercise tolerance has been identified as a
strong predictor of perioperative complications and functional recovery. Besides
lifestyle modifications and nutritional support, implementing pre- and
postoperative muscle training is grounded on strong experimental data and
should be considered to downgrade high-risk patient into a lower-risk profile.
In 2016, emerging data indicate that short-term physical training prescribed
in patients awaiting lung cancer resection results in a consistent increase in
aerobic capacity (average +10–20 % VO2max, increase walking distance).
However, the current evidence for exercise-induced clinical improvement is
skewed toward small RCTs or cohort studies with relatively fit patients,
undergoing mostly generalized (“one size fits all”) moderate-to-high-intensity
exercise programs that are neither targeted to achieve significant improvement in
aerobic fitness nor tailored to the patient’s own abilities. Moreover, studies
largely differ regarding type, dose, and timing of physical interventions.
Future research should identify which aspects of exercise training programs
(strength, endurance, or functional mobility) are appropriate and tolerable for
each individual and specific group of patients. Moreover, exercise training-
related research should also incorporate monitoring principles to establish the
optimum in training parameters. High-intensity training is likely necessary to
achieve improvements given the often short time available before surgery.
Fortunately, even frail and older patients can tolerate these specific programs.
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DOI 10.1007/978-3-319-19908-5_19
19. Perioperative Care of Thoracic Trauma

Patient
Kemalettin Koltka1

Kemalettin Koltka
Email: ahmetkoltka@yahoo.com
19.1 Introduction
Trauma is one of the leading causes of death in the world. Thoracic trauma
accounts for 20–25 % of the trauma mortality; in these cases, cardiac trauma or
the rupture of great vessels is the main reason of immediate mortality.
Penetrating and blunt traumas are the two mechanisms for thoracic trauma;
the mechanism is important: if a patient has a penetrating thoracic trauma (stab
wounds, gunshot wounds, etc.), searching an injury in the tracheobronchial tree
is the first priority in the initial examination of the patient.
In blunt trauma, traffic road accidents and falls are the most frequent
mechanisms of injury [1]. In a series of 22613 patients, Huber et al. found that
nearly half of the cases had pulmonary contusion (10864, 48 %); pneumothorax
(8878, 39 %), rib fractures (7794, 35 %), hemothorax (6223, 28 %), flail chest
(3681, 16 %), and lung laceration (2644, 12 %) are the other common injuries
following thoracic trauma [1].
Blunt or penetrating thoracic trauma can cause injury to the larynx,
tracheobronchial tree, lungs, or chest wall. The incidence of extrathoracic
injuries associated with major blunt trauma is high; in most cases head trauma
(cerebral concussion, cerebral contusion, skull fracture, facial fractures), lower
and/or upper extremity injuries, and abdominal injuries are also present [2]. This
chapter will focus on blunt thoracic trauma and the common diagnosis/problems
after blunt thoracic trauma. As anesthesiology contains the perioperative period,
an anesthetist can meet the thoracic trauma patient in the emergency department,
in the operating rooms, in the ICU, and in the algology department, and the
thoracic trauma patient will be discussed according to this fact.
19.2 Traumatic Pneumothorax

Pneumothorax is one of the most common manifestations of thoracic trauma and
may be noted in 40–50 % of patients with chest trauma [3]. Unfortunately a huge
number of pneumothoraces are occult and cannot be seen on an initial chest x-
ray but found later by additional imaging. The high incidences of occult
pneumothoraces emphasize the early routine CT in all polytrauma patients. CT
scan can detect not only pneumothorax but also other complications, including
lung contusion, diaphragmatic rupture, and hemothorax. Detecting
pneumothorax is critical, given the likelihood of pneumothorax progression if
mechanical ventilation or anesthesia is required.
The use of ultrasonography is increasing for pneumothorax evaluation.
Ultrasonography is especially important in unstable trauma patients whose
transport for CT scans is not possible.
The etiology of the development of a pneumothorax in blunt chest trauma in
the absence of a rib fracture lacerating the visceral pleura is not very clear. A
sudden increase in alveolar pressure can lead to alveolar rupture and dissection
of air into the interstitium of the lung that may then dissect to the visceral pleural
surface and to the mediastinum. The rupture of the visceral pleura or mediastinal
pleura may lead to a pneumothorax [3].
The treatment of choice in a traumatic pneumothorax is the placement of a
chest tube. In the presence of known hemothorax or mechanical ventilation, a
large-bore chest tube (28–36 F) must be used; most clinicians will recommend
immediate placement of a large-bore chest tube in all patients with a traumatic
pneumothorax [3].
The treatment of choice in occult pneumothoraces is less clear although most
occult pneumothoraces likely do not warrant the potential risk associated with a
tube thoracostomy. If there is a need of positive-pressure ventilation or there is
an accompanying hemothorax, then a chest tube placement must be considered.
Chest tube placement not only evacuates air and blood but also can be used as a
monitor of the rate of blood loss which can be a reason for immediate operative
intervention [3].
19.3 Hemothorax
Massive hemothorax is defined as a rapid accumulation of more than 1.500 ml of
blood in the pleural space. Such a huge hemothorax can be due to large
pulmonary lacerations and great vessel or intercostal vessel injury [4]. A
hemothorax can accommodate nearly half of the total blood volume. A massive
hemothorax may induce hemodynamic instability due to the loss of intravascular
volume and respiratory compromise due to mass effect. A trauma patient in
shock, associated with the absence of breath sounds and/or dullness on one side
of the chest, should be treated for massive hemothorax until proven otherwise
[4]. Volume resuscitation and placement of a large-bore chest tube are initial
treatment modalities, and these will be the adequate treatment for most of the
cases. Bleeding generally stops in a few minutes after lung expansion. An initial
drainage of > 1.500 ml blood from the chest tube or > 250 ml/h drainage for
more than 3 consecutive hours or a drainage requiring blood transfusion is the
main indication for operation [4].
19.4 Pulmonary Contusion

Pulmonary contusion is a common result of major trauma [1]. Although thoracic
injuries among children are uncommon, 50 % of such lesions involve pulmonary
contusion [5].
The clinical manifestations of pulmonary contusion may be insidious; the
initial chest x-ray may be normal, and respiratory difficulty may become evident
hours after injury. Patients who sustain pulmonary contusions have higher risks
of pneumonia and acute respiratory distress syndrome (ARDS) and long-term
respiratory disability. The outcomes of pulmonary contusions appear to be
similar for pediatric and adult age groups [6].
Patients who have experienced trauma involving high-energy transfer should
be evaluated for pulmonary contusion because prompt diagnosis and
intervention may improve outcome [6].
It is difficult to diagnose pulmonary contusion with chest x-ray; only half of
the lesions are detected at the initial chest x-ray, whereas 92 % of pulmonary
contusions can be seen 24 h after the trauma. Enlargement of lung contusions on
chest x-ray during the first 24 h is generally a sign of bad prognosis.
Furthermore, the degree of contusion can be hard to separate clinically from the
effects of aspiration, fluid overload, transfusion-related acute lung injury
(TRALI), and pulmonary embolism [6].
CT scan of the thorax is currently the standard of care for the diagnosis and
risk stratification of pulmonary contusions. However, there are many patients
with pulmonary contusions found at CT scans and without physiologic
deterioration, and some authors have suggested that newer CT scans are overly
sensitive in this situation.
19.4.1 Treatment
The treatment of pulmonary contusion is primarily supportive: supplemental
oxygen and rapid assessment of airway and breathing should be done according
to standard trauma protocols. Pulmonary contusions may be associated with
severe hypoxemia, so patient transport can be hazardous even in the prehospital
setting.
In the emergency department, patients with pulmonary contusions are
examined and treated according to modern trauma care protocols. Although
uncommon, in patients with unilateral pulmonary contusions and/or massive
intratracheal bleeding or in patients having severe air leaks, selective intubation
is useful. Endobronchial blockers are useful in controlling hemoptysis in patients
with diffuse pulmonary contusions [6]. Blockers are also used to protect the
uninjured lung from blood and decrease the risk of air embolization. They also
avoid the changing of endotracheal tubes which can be a risky procedure due to
difficult intubation and problems due to trauma. But it should be kept in mind
that most of the anesthetists are more familiar with the double-lumen tubes for
one-lung ventilation.
Regarding the use of the devices for one-lung ventilation, one has to be
aware to differentiate “lung isolation” and “lung separation.” “Lung isolation” is
rather a method to prevent the non-diseased lung from the contamination (such
as massive bleeding, pus, etc.) of the diseased one. Therefore, it should be
underlined that in “emergency” cases, lung isolation can play a more important
role than lung separation. For lung isolation, double-lumen tubes are considered
to be more appropriate, while blockers are designed more for the lung
separation. On the other hand, the recently introduced EZBlocker can be a
rational alternative, for it is easy to manage, can be used to block both lungs
consequently, and can be positioned even if no fiber-optic bronchoscopy is
available.
Anesthesiologists/intensivists should be familiar with the use of fiber-optic
bronchoscopy (FOB) also in the emergency units. FOB should be considered as
a very important part of not only the general management of the thoracic trauma
patient, such as (not exclusively):
Diagnosis and aspiration of blood and pus in the major airways
Diagnosis of problems in airway integrity
Lung isolation
Lung separation during operation
Aggressive pulmonary toilet, meticulous fluid management, and an effective
pain control therapy using multimodal analgesic techniques (especially regional
techniques such as epidural and paravertebral blockades) are the cornerstones of
treatment.
Noninvasive positive-pressure ventilation (NPPV) may be appropriate for
selected patients with pulmonary contusion and hypoxemia. In a prospective
evaluation of 2.770 patients with hypoxemic acute respiratory failure, NPPV was
successful in patients with cardiogenic pulmonary edema (90 %) and pulmonary
contusion (82 %); the success rate for patients with acute lung injury (ALI) was
only 10 % [7, 8].
If endotracheal intubation is necessary, mechanical ventilation strategies
should aim the optimization of oxygenation while avoiding secondary injuries.
Limiting peak and plateau pressures and the use of low tidal volumes and
avoiding overdistension are the cornerstones of ventilation strategies in patients
with pulmonary contusions. Pressure-controlled ventilation minimizes peak (but
not plateau) airway pressures and “may” help prevent barotrauma. Lung
contusions usually begin to resolve in 2–5 days after trauma if other pulmonary
complications are not superimposed [4]. In some cases permissive hypercapnia
or alveolar recruitment maneuvers can be necessary, but these techniques must
be used cautiously in patients having head trauma.
Pulmonary parenchymal repair or resection, including thoracotomy and
repair, wedge resection, lobectomy, or pneumonectomy, is required in less than
2% of blunt thoracic trauma patients [9].
Pulmonary contusion should always be considered when there is an
unexpectedly high alveolar-arterial PO2 difference in the course of resuscitation
from or surgical repair of any thoracic injury. Rib fractures are often associated
with pulmonary contusion in the area adjacent to the fractures. Pneumonia and
ARDS may occur with subsequent long-term disability [4].
With the increase of our knowledge about the pathophysiology of
hemorrhagic shock, innovative resuscitative approaches have emerged.
Hypertonic saline has been shown to effectively restore perfusion after
hemorrhagic shock, and the volume requirement is smaller than that for
traditional high-volume isotonic alternatives or blood product-based approaches
[10]. This treatment modality was used by several authors for thoracic trauma,
but no clinical studies have demonstrated a pulmonary physiologic benefit from
the use of hypertonic saline after thoracic trauma [6].
There is not enough data about the long-term impacts of pulmonary
contusion on quality of life of survivors. In a small series of patients with flail
chest who had or did not have pulmonary contusion, persistent abnormalities in
functional residual capacity (approaching closing volume) and oxygenation were
found after lung contusion. Patients with pulmonary contusion, but not those
with flail chest alone, frequently exhibited disabling dyspnea. Subsequent chest
CT scans revealed fibrosis in the lungs of pulmonary contusion patients with
dyspnea [11]. The authors of a long-term follow-up on 55 patients with multiple
trauma associated with blunt chest trauma found out that the pulmonary function
tests were impaired and physical function was decreased in 70% of patients,
resulting in reduced pulmonary-specific quality of life [12].
In children the prognosis is much better; in a long follow-up investigation of
pediatric patients with pulmonary contusion, the results showed unremarkable
chest x-rays and normal lung function, and the authors concluded that children
who recover after a pulmonary contusion-laceration trauma do not suffer from
significant late respiratory problems [13].
19.5 Rib Fractures

Rib fractures are one of the most common injuries found in blunt chest trauma
patients [1]. In a textbook, the incidence of rib fractures after blunt trauma is
stated as 60% [14]. The ribs typically involved are IV–X. If the first two ribs are
broken, the patient had suffered a high-energy trauma, and as these ribs provide
protection to vital structures, lesions of the brachial plexus and vessels
(subclavian artery and vein) may occur, and pulmonary contusions are likely
[14]. If the lower ribs are broken, injuries to the abdominal organs such as the
liver, spleen, and kidneys must be sought. The fractures of the lower ribs are
generally due to direct local trauma. In the elderly population, even minor
traumas often result in rib fractures due to osteoporosis and decreased bone
elasticity [14].
Rib fractures cause two important problems: chest wall pain and pulmonary
lacerations. Untreated or poorly treated chest wall pain leads to reduced
ventilation with and subsequent complications such as pneumonia and
atelectasis. Pulmonary lacerations may cause pulmonary hematoma,
hemothorax, and pneumothorax.
Serial rib fractures are defined as the fracture of at least three ribs and occur
in almost one third of all rib fracture cases. As the number of rib fractures
increases, the risk for developing a flail chest also increases.
Flail chest is a common result of blunt chest trauma and occurs in 16% of
patients with blunt chest trauma [1]. There are different definitions of flail chest:
at least five contiguous single rib fractures or three adjacent segmental rib
fractures or at least two adjacent ribs are broken in at least two places [14, 15].
This results in an unstable flail segment with a paradoxical respiratory motion
(inward motion during inspiration and outward motion during expiration).
Posterior flail segments are stabilized by overlying muscles as well as the
scapula and therefore may not cause severe complications. In contrast, anterior
and lateral flail segments are mobile and can seriously impair respiratory
function. Additionally, a flail chest is generally associated with a lung contusion
[16].
19.5.1 Acute Pain Management of Patients with Multiple

Fractured Ribs
Patients with multiple fractured ribs (MFR) have severe pain that adversely
affects a patient’s ability to cough and breathe deeply, predisposing the patient to
sputum retention and respiratory insufficiency. Effective analgesia, chest
physiotherapy, and respiratory care are the cornerstones of management.
Effective analgesia is vital because it allows patients to breathe deeply, cough
effectively, and comply with chest physiotherapy [17].
There are many analgesic options available for pain treatment in patients
with MFR. If the number of ribs fractured is low and the patient is young and
without other major comorbidities, systemic analgesics may suffice.
Nonsteroidal anti-inflammatory drugs (NSAID), codeine, or paracetamol can be
used for effective pain treatment, and patients can be discharged from the
hospital safely with these medications. Generally in the acute phase, a strong
opioid such as morphine is added to the treatment. Ketamine is a good option for
analgesia supplementation. Both opioids and ketamine can be given in the
prehospital setting [18]. If the patient has a concomitant head trauma and the
observation of his/her level of consciousness is mandatory, then strong opioids
or ketamine is no longer a desired option. In such cases regional techniques can
be used as the main analgesic modality.
For older patients (>65 years of age) and for patients with ≥ 4 fractured ribs,
regional techniques are better choices of analgesia [18]. Furthermore, underlying
lung injury may not manifest early in plain chest x-rays. As such, regional nerve
block should be considered in all patients when there is significant pain and/or
the respiratory status is unstable.
19.5.2 Thoracic Epidural Analgesia

Thoracic epidural analgesia (TEA) can be used in these patients because it
provides good pain relief, and the improvements in respiratory functions are
better than intravenous opioid patient-controlled analgesia [19, 20].
In patients with bilateral MFR, TEA is the technique of choice; thoracic
epidural catheter must be inserted close to the middle level of the fractured ribs.
An example of TEA protocol in trauma patients: After a test dose of 3 ml of
2.0% lignocaine with epinephrine (1:200.000), 0.5% bupivacaine in a volume of
1 ml/segment to 1.5 ml/segment can be administered as bolus followed by an
infusion of 0.125% bupivacaine at a rate of 0.1 ml/kg/h to 0.2 ml/kg/h [21]. The
elderly patients are the group of patients who will benefit the most from TEA
because the mortality due thoracic trauma is higher in this group of patients than
their younger counterparts. Contraindications of TEA in trauma patients include
vertebral fracture, hemodynamic instability, and traumatic coagulopathy. In
elderly patients, to have information about previous medications is mandatory:
many elderly patients are using anticoagulant or antiplatelet agents. TEA has
also been associated with prolonged length of stay and increased complications
in elderly patients [22].
19.5.3 Thoracic Paravertebral Block

Unilateral thoracic paravertebral block (TPVB) is a good alternative to TEA in
patients with MFR or to patients undergoing thoracotomy [21, 23]. TPVB has
been found to be a simple and an effective method of providing continuous pain
relief in patients with unilateral MFR [17]. It is technically less complex with a
few absolute contraindications [24]. Specifically, the block can be performed
(and the catheter withdrawn) in the presence of even a moderate degree of
coagulopathy which is frequently present in polytrauma patients. Hypovolemia
and hypotension are not absolute contraindications, because TPVB is associated
with minimal hemodynamic problems. Opioids are infrequently used, so risks
like urinary retention and pruritus are very low. Epidural and intrathecal drug
administration and pneumothorax are the complications of the technique, but the
incidences are low. Local anesthetic toxicity is possible, if more than one
catheter is used such as in bilateral blocks [25].
An example of TPVB: After a test dose of 3 ml of 2.0% lignocaine with
epinephrine (1:200.000), a bolus dose of 0.5% bupivacaine in a volume of 0.3
ml/kg (1.5 mg/kg) was injected, and this was followed by a continuous infusion
of 0.25% bupivacaine at a rate of 0.1 ml/kg/h to 0.2 ml/kg/h [21].
In their study comparing TPVB with TEA in unilateral MRF patients, Mohta
et al. concluded that continuous bupivacaine infusion through TPVB is as
effective as through TEA for pain management in patients with unilateral
fractured ribs and the outcome after two techniques is comparable [21].
19.5.4 Intercostal Nerve Block

Intercostal nerve block (ICNB) is an effective block; the main disadvantage of
this block is the necessity for multiple injections at each of the levels and one
level above and one below the fractured ribs. The block is generally effective for
4–8 h when a long-acting local anesthetic or epinephrine-local anesthetic
combination is used [25]. The block is technically easy and simple to perform. A
major disadvantage of ICNB is the necessity for repeated multiple injections
which makes this cheap, easy, and effective analgesic modality a secondary
option for MFR patients. However, a higher number of injections increase the
risk of pneumothorax, intravascular injection, and local anesthetic toxicity.
To increase the effectiveness and utilization of ICNB, novel techniques were
investigated: Truitt et al. placed two multiport catheters in an extrathoracic
paraspinous location to create a continuous intercostal nerve block and started an
infusion of 0.2 % ropivacaine at a constant rate of 14 ml/h in total (7 ml in each
catheter) and achieved excellent analgesia, improvements in pulmonary
functions, and a decreased length of stay when compared with historic controls
[26]. Moving the scapula as lateral as possible and using ultrasound or
fluoroscopy may facilitate ICNB at the upper thoracic levels [25]. Depending on
the location of the rib fractures, ICNB can be performed at the angle of the rib
(5–8 cm from midline in adults) or at the posterior axillary line. When ICNB
was performed immediately lateral to the paraspinal muscles, the epidural
catheter can be send toward the midline to effect a continuous TPVB without the
disadvantages of multiple and repeated injections [27].
19.5.5 Interpleural Block

Interpleural analgesia has been evaluated for multiple uses, including multiple
rib fracture patients [28]. Interpleural block was compared with intercostal nerve
block, and the latter technique was better [29, 30].
The block is easy to perform when clear landmarks are present and usually
involves the placement of a continuous catheter for infusion. The technique can
be performed percutaneously, and a posterior approach is a better choice. The
amount of local anesthetic injected can vary from 10 to 30 ml, and most will
select a 20 ml of 0.25%–0.5% bupivacaine with epinephrine [31].
Pneumothorax, local anesthetic toxicity, unilateral Horner’s syndrome, and
phrenic nerve blockade are the complications of interpleural block.
Preexisting pleural effusions or hemothorax can be accepted as relative
contraindication, because the fluid will make diffusion of the local anesthetic
unpredictable and diminish the efficacy of the block. Infection at the insertion
site or within the pleural cavity is an absolute contraindication of interpleural
block [31].
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DOI 10.1007/978-3-319-19908-5_20
20. Chronic Obstructive Pulmonary

Disease and the Postoperative Period
Gary H. Mills1
(1) Sheffield Teaching Hospitals and University of Sheffield, Sheffield, UK

Gary H. Mills
Email: g.h.mills@sheffield.ac.uk
20.1 Introduction
Chronic obstructive pulmonary disease (COPD) is encountered during thoracic
surgery in four broad circumstances: (1) during one-lung anesthesia for
lobectomy or removal of a lung in a patient who is/was usually a smoker and has
developed lung cancer, (2) during lung volume resection surgery in emphysema
or (3) bullectomy as a treatment for large bullae which are causing dyspnea or
are at risk of causing pneumothoraces, and (4) in patients with COPD who may
undergo lung transplantation.
Mortality after thoracic surgery is relatively high. When considering surgery
for lung cancer, the mortality rates for lobectomy are 4 and 11.5 % for
pneumonectomy. Postoperative pulmonary complications include air leak,
pneumonia, bronchopleural fistula, and acute respiratory failure. ARDS or
barotrauma may occur, often in the nonsurgical lung. Long operating times and
the need for postoperative mechanical ventilation greatly increase the likelihood
of complications [1].
20.2 Which Factors Suggest Postoperative

Complications in Patients with COPD?
Although COPD is an independent risk factor for perioperative complications in
major surgery, somewhat surprisingly specific lung function test values in COPD
alone have not been a good predictor of postoperative complications. However,
certain closely related factors are important, such as low preoperative SpO2 or
recent pulmonary infection as seen in ARISCAT [2], especially in prolonged
abdominal surgery and even more so in thoracic surgery. One study suggests
perioperative risk may be increased by COPD with a preoperative FEV1 <70 %
predicted or FEV1/FVC ratio <65 % [3]. Diffusing capacity for carbon
monoxide is also a guide to severity of emphysematous change in the lung in
moderate and severe COPD. Some recent studies have also confirmed COPD as
an independent risk factor. In a recent analysis of over 300,000 patients
(including 1200 with COPD) in the National Surgical Quality Improvement
Program database undergoing abdominal surgery, COPD was independently
associated with increased postoperative morbidity and with increased length of
stay and mortality in some types of surgery [4]. Postoperative respiratory failure
is more common in COPD [5], as is postoperative pneumonia [6]. Surgery
during an exacerbation of COPD poses high risks and should only be entertained
in an emergency situation. Patients should be optimally treated, until they settle
back to baseline lung function. This treatment would normally involve steroids,
which – if prolonged – will necessitate additional steroids to reduce the risk of
adrenal suppression when surgery is eventually undertaken.
Pulmonary risk during lung resection is associated with abnormal
preoperative lung function tests including a preoperative FEV1 under 60 % of
predicted in lung resection surgery. DLCO is also useful in predicting risk [7, 8].
Low-risk groups include those with a preoperative FEV1 and DLCO of over 80
% predicted. Predicting postoperative pulmonary function is also important and
has involved using formulas such as below that examine the amount of the lung
to be resected and its functional contribution.
Predicted postoperative FEV1 (PPOFEV1) = Preoperative FEV1 × (1-
(number functional lung segments being removed/total number of functional
lung segments, which may be 19)).
One study has suggested that a predicted postoperative FEV1 value and
DLCO of >40 % of the predicted normal preoperative values were not associated
with mortality. Guidelines from the European Respiratory Society and European
Society of Thoracic Surgery use a predicted postoperative FEV1 or DLCO of
>30 % as the cutoff, below which death is a likely outcome [9]. Between 60 and
30 % may suggest that exercise testing such as a stair climb or shuttle test is
required to better delineate the risk. More precise assessment would involve
cardiopulmonary exercise testing. VO2 max <15 ml/kg produces a high risk of
complications [10]. If the predicted postoperative (PPO) VO2 is likely to be <10
ml/kg, then resection is likely to result in death. Traditional tests such as stair
climbing are effective, but unfortunately stairs are not standardized; however,
being able to climb less than 12 m increased complications including death [11].
20.3 Preoperative Physiotherapy or Cardiopulmonary

Rehabilitation and Their Impact on the Postoperative
Period in COPD
It is important to reduce the postoperative risks in COPD patients by whatever
means have been shown to be effective, as postoperative complications are
common in patients undergoing one-lung anesthesia especially for lung resection
surgery [12–17]. Unfortunately most work in this area has been conducted on
abdominal and cardiac surgery and generally in patients without COPD.
However some evidence is available, especially prior to lung volume reduction
surgery, lung transplant, and, to a lesser extent, prior to lung resection for lung
cancer. Preoperative pulmonary rehabilitation improves exercise capacity and
dyspnea. One study has looked at the impact on moderate to severe COPD
undergoing lung resection due to cancer. Prolonged rehabilitation lasting 1
month proved very difficult to deliver, whereas a ten-session program (including
lower extremity endurance training for 20 mins, upper extremity endurance
training, strengthening exercises, inspiratory muscle training, and slow
breathing) was much more practical and appeared to reduce length of stay and
shortened chest drain duration [18].
Despite the inherent potential delay to surgery, several studies have managed
to look at pulmonary rehabilitation for 4 weeks prior to lung cancer resection.
They have shown a reduction in postoperative respiratory morbidity, including a
study by Cesario [19] and an observational study by Bobbio [20]. Unfortunately
in one study of lung resection, the patients in the pulmonary rehabilitation arm
had a better baseline maximal inspiratory and expiratory pressure [21], which
could have influence their future outcomes.
The ability of COPD patients to exercise may not just be related to lung and
cardiovascular performance. COPD patients may be unable to exercise because
of limb weakness that has occurred secondary to a lack of mobility caused by the
lung disease [22, 23]. Some exercise programs can overcome this and produce
an improvement in walking distance, dyspnea, pulmonary functional status scale
[24], cardiovascular fitness, and leg muscle strength. This then benefits patients
in the postoperative period.
20.4 Smoking, COPD, and Postoperative Recovery

COPD is most commonly caused by smoking. Therefore many patients with
COPD undergoing surgery are still smokers, which is likely to increase
postoperative complications [25]. Smoking cessation 8 weeks prior to surgery
appears to be beneficial, improving pulmonary outcomes and wound healing [26,
27]. Frequently, patients will require surgery in less than 8 weeks. It is often
thought that stopping smoking close to surgery causes a worsening of pulmonary
postoperative complications; however, the evidence for this is not strong [28].
Smokers undergoing surgery will need to stop in the immediate postoperative
period, because of the safety requirements of supplemental oxygen. So any
concern that stopping may produce respiratory secretions and related issues
should not stop a patient from trying to cut down or quit prior to surgery.
Consideration of the need for nicotine patches may be important in the
postoperative period.
20.5 COPD in Non-thoracic Surgery

Operations on the thorax or upper abdomen are likely to significantly reduce
functional residual capacity. How can this problem be reduced? If a patient can
lie flat or in a suitable position for surgery, then a peripheral nerve block (such as
in ophthalmic surgery) and regional or spinal/epidural analgesia/anesthesia are
likely to have a lesser impact on the lung. General anesthesia using techniques
that avoid intubation will reduce related bronchospasm. Unfortunately this will
not be suitable for most major surgery. Laparoscopic techniques reduce
postoperative pain, which is also helpful in COPD. However insufflation of CO2
and the compressing effect of gas passed into the abdomen or thorax will add a
load onto the respiratory system and contribute to atelectasis.
Induction agents including propofol obtund laryngeal and tracheal reflexes
and ketamine has bronchodilator properties. During maintenance, sevoflurane is
a good bronchodilator. Desflurane has rapid emergence, which may be helpful.
Opioids need to be used carefully to avoid respiratory depression, especially in
patients who are already CO2 retainers. The combination of epidural anesthesia
and general anesthesia reduces the incidence of postoperative pneumonia from
16 to 11 % and mortality from 9 to 5 % [29].
20.6 Mechanical Ventilation
Air trapping is a potential major issue in one- and two-lung anesthesia, leading
to dynamic hyperinflation, which produces raised intrathoracic pressure in the
intraoperative period, with potential respiratory and cardiovascular consequences
during and after surgery. This can be visualized as failure to complete exhalation
on the monitored flow time graph. Increased expiratory time can be provided by
decreasing inspiratory time, increasing I/E ratio, and slowing respiratory rate.
Air trapping can become severe, producing an elevation of intrathoracic
pressure, which may even require temporary disconnection from the breathing
circuit to allow the trapped air to escape. Application of some PEEP may hold
airways open during expiration if set to levels equivalent to intrinsic PEEP.
However pressures and the tendency to air trapping may vary in different parts
of the lung, so the applied PEEP may not suit all lung units and a relatively low
PEEP may be more effective in patients with bronchospasm. High FiO2 leads to
absorption atelectasis [30], which appears rapidly after induction of anesthesia
[31, 32], becoming exponentially more of an issue when we consider time to
increase in atelectasis, especially at end-tidal oxygen levels 90 % and above
[33]. This is made even worse in patients with poor V/Q mismatch [34].
However, in the postoperative period, the importance of limiting inspired oxygen
concentrations to avoid atelectasis is in some doubt [35], although some have
postulated this confusion in the evidence is because of the use of high FiO2
levels earlier in the anesthesia [34]. However, there are times in COPD when
administration of a high FiO2 may cause problems in patients with a raised
PaCO2, which may lead them to retain even more PaCO2. Lung protective
ventilation during surgery is also important and is dealt with in a separate
chapter.
Duration of surgery is very important with a postoperative pneumonia rate of
8 % in operations lasting under 2 h, rising to 40 % for operations over 4 h in
length [36]. Complete reversal of neuromuscular blockade is essential to avoid
postoperative pulmonary complications [36, 37, 38, 39].
Patients with postoperative lung injury, especially after thoracic surgery, may
have a huge increase in mortality (up to 39 %) at 30 days [40]. During one-lung
anesthesia, lungs are subject to deflation, atelectasis, reinflation, and the effects
of released inflammatory mediators, as well as the threat to anastomoses in terms
of airway pressure, vascular supply, and healing.
20.7 Postoperative Interventions
Thoracic, abdominal, and aortic aneurysm surgeries are frequently complicated
by postoperative pulmonary complications. Studies have looked at techniques
and exercises that can be introduced or taught to patients in the preoperative
period, which can be continued after surgery. Unfortunately, most of these
studies have not involved thoracic surgery patients. Despite this, there are some
areas where basic principles appear to make a difference. These include
mobilization and adequate pain relief. Less invasive surgery can help here.
Studies on major abdominal surgery have concluded that postoperative
complications including postoperative pneumonia and 30-day mortality are
reduced in patients with COPD when thoracic epidural analgesia is used [29].
Early mobilization reduces postoperative pulmonary complications, whereas
slow mobilization adds risk with each day of delay [41]. The greatest first day
barrier to mobilization was hypotension.
Patients with malnutrition or who have a low albumin are at risk of
postoperative complications, and this may require intervention both before and
after surgery.
20.8 Continuous Positive Airway Pressure

Continuous positive airway pressure (CPAP) has good theoretical advantages
after surgery, in that it can increase transpulmonary pressure, improve functional
residual capacity, expand collapsed areas, and improve gas exchange. Most
studies have looked at major abdominal and cardiac surgeries. Comparisons
between very brief periods of CPAP versus 6 h continuous CPAP have shown
reduced incidence of pneumonia and re-ventilation with the more sustained
treatment [42]. Similarly postoperative CPAP after major abdominal surgery has
been shown to reduce atelectasis, pneumonia, and reintubation [43].
20.9 Noninvasive Ventilation

Noninvasive ventilation (NIV) could theoretically be useful after thoracic
surgery, especially if CO2 retention is present. One concern with both CPAP and
NIV is whether there will be an increased incidence of air leaks (air leaks are
relatively common after pulmonary lobectomy at around 9.7 %). Fortunately the
small number of studies performed on thoracic surgery patients does not appear
to have found an increase [44, 45]. NIV has been used after thoracic surgery and
has been found to increase arterial oxygenation.
20.10 Simpler Techniques for Improving Oxygenation

Deep breathing exercises and incentive spirometry may be effective in the post-
op care of thoracic surgery patients and have the advantage that they can be
quickly taught to patients both pre- and post-op [46]. Unfortunately, clinical
studies in upper abdominal surgery have not been conclusive in showing major
benefits [47, 48].
20.11 Lung Volume Reduction Surgery (LVRS) in

COPD
Loss of elastic tissue and alveolar walls in emphysema leads to hyperinflation.
This puts the respiratory muscles at a mechanical disadvantage during
inspiration, especially the diaphragm which in extreme cases becomes flattened
and unable to descend effectively during inspiration [49]. Therefore if patients
can be selected who will gain elastic recoil following surgery, the likely outcome
is an improvement in dyspnea and exercise capacity [50]. The reduction in
extreme stretch on the lung may also reduce pulmonary vascular resistance.
Most LVRS is performed via thoracotomy or median sternotomy. A
thoracoscopic approach is also common and more recently bronchoscopic
techniques have been developed.
Perioperative mortality and morbidity in LVRS is best reduced by excluding
patients from surgery in the first instance with an FEV1 and homogenous
emphysema of ≤20 % predicted or a DLCO ≤20 % predicted. Perioperative
complications include persistent air leak, reintubation possibly with prolonged
ventilation, respiratory failure, pneumonia, arrhythmias, myocardial infarction,
pulmonary embolism, and bleeding. Prior to surgery, most patients will have
undergone extensive pulmonary rehabilitation, treatment of COPD, and any
other underlying conditions. Postoperatively, bronchospasm will be treated and if
ventilator failure occurs, NIV commenced. Most air leaks settle with pleural
drainage, but around 3 % persist and re-exploration may be needed. Hemorrhage
requiring re-exploration occurs in around 1 %.
20.12 Bullectomy and COPD

Giant bullae occupy more than 30 % of a hemithorax. They are most commonly
caused by smoking, occasionally are associated with marijuana and intravenous
drug abuse. They may also occur in association with alpha-1 antitrypsin
deficiency. Rarely, they occur with Marfans and Ehlers-Danlos syndrome and
sarcoidosis. They make breathing less efficient and sometimes produce a
secondary spontaneous pneumothorax. Postoperatively complications are similar
to LVRS.
Conclusion
Care of patients with COPD in the postoperative after lung surgery relies to
some extent on evidence gathered during the study of other types of major
surgery. More study specific to thoracic anesthesia is needed. However, most
problems that develop in the perioperative period can most effectively be dealt
with by good preoperative assessment, selection, and preparation. This
preparation will involve respiratory rehabilitation. Early postoperative
mobilization is important. Good pain relief is also vital. Epidural analgesia has
been shown to reduce the incidence of pneumonia.
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Index
A
Acetylcholine receptor (AChR)
Acute cardiogenic pulmonary oedema
Acute kidney injury (AKI)
Acute lung injury (ALI)
“baby lung” concept
clinical forms
postoperative
classification
fluid administration
incidence
multiple-hit model
risk factors
protective ventilation
Acute Physiology and Chronic Health Evaluation (APACHE) score
Acute respiratory distress syndrome (ARDS)
diabetes mellitus
mortality rate
multiple-hit hypothesis
NPPV
postoperative
protective ventilation
VATS
Acute respiratory failure (ARF)
Adult respiratory distress syndrome
Airway closure
Airway complications
ALI
See Acute lung injury (ALI)
Alveolar recruitment maneuvers (ARMs)
American College of Critical Care Medicine (ACCM)
American Society of Anesthesiologists’ (ASA)
Analgesia
multimodal
preemptive
regional
continuous wound catheter analgesia
cryoanalgesia
intercostal and interpleural block
PVB
TEA
systemic
acetaminophen
gabapentin
ketamine
NSAID
opioids
pregabalin
selective alpha-2-adrenergic receptor agonist dexmedetomidine
Anastomosis dehiscence
Anastomotic leak
Anastomotic stricture
Anti-AChE therapy
Antibiotic prophylaxis
Antiplatelet agents (APA)
characteristics
chronic treatment
haemorrhagic risk
indications
management
direct oral anticoagulant
vitamin K antagonists
protocols
recommendations
thromboprophylaxis
general measures
mechanical methods
perioperative period
pharmacological methods
rationale
thrombotic risk
Anxiety
APA
See Antiplatelet agents (APA)
ARDS
See Acute respiratory distress syndrome (ARDS)
ARF
See Acute respiratory failure (ARF)
Aspiration pneumonitis
Assess respiratory risk in surgical patients in catalonia (ARISCAT) Score
Atelectasis
anesthesia
definition
early pulmonary physiotherapy and nasotracheal aspiration
endobronchial aspiration and lavage
formation
occurence
PEEP
predisposing factors
recruitment maneuver
smoking
symptoms
Thoracic Surgery Database
Atrial fibrillation
amiodarone iv
beta-blockers
class I antiarrhythmic drugs
digitalis
incidence
nondihydropyridine calcium channel antagonists
prevention
risk stratification
B
Basal pyramid torsion
Beta-blocker
Blunt trauma
Body mass index (BMI)
Bradyarrhythmias
Bronchial blocker (BB)
Bronchial colonization-airway colonization
Bronchoalveolar lavage (BAL)
Bronchomediastinal fistula
Bronchopleural fistula (BPF)
Bronchospasm
Bronchovascular fistulas
Bullectomy
C
Cardiac arrhythmias
atrial fibrillation
amiodarone iv
beta-blockers
class I antiarrhythmic drugs
digitalis
incidence
nondihydropyridine calcium channel antagonists
prevention
risk stratification
bradyarrhythmias
negative implications
patient-related risk factors
surgery-related risk factors
Cardiac herniation
Cardiac tamponade
Cardiopulmonary exercise testing (CPET)
Cardiopulmonary rehabilitation
Cardiopulmonary risk index (CPRI)
Central venous oxygen saturation (ScvO 2 )
Central venous pressure (CVP)
Cholinergic crisis
Chronic obstructive pulmonary disease (COPD)
bullectomy
cardiopulmonary rehabilitation
CPAP
deep breathing exercises
incentive spirometry
LVRS
mechanical ventilation
NIV
in non-thoracic surgery
postoperative interventions
postoperative recovery
preoperative physiotherapy
risk factor
smoking
Chronic postthoracotomy pain syndrome (CPTP)
Chronic thromboembolic pulmonary hypertension (CTEPH)
Chylothorax
Comprehensive geriatric assessment (CGA)
Conduit ischemia
Congestive heart failure (CHF)
Continuous positive airway pressure (CPAP)
Continuous wound catheter analgesia
COPD
See Chronic obstructive pulmonary disease (COPD)
Corticosteroid therapy
Cryoanalgesia
Cyclosporine therapy
D
Deep breathing exercises
Deep vein thrombosis (DVT)
Descending flow pattern
Differential lung ventilation (DLV)
Diffusing capacity of the lung for carbon monoxide (DLCO)
Digoxin
Direct oral anticoagulant (DOAC)
Double-lumen tube (DLT)
Driving pressure (DP)
Duke Activity Status Index
Dumping syndrome
E
Echocardiography
intravascular volume status
pericardial effusion
pulmonary embolism
thoracic trauma
valvular function
ventricular function
ECMO
See Extracorporeal membrane oxygenation (ECMO)
Edrophonium test
Electric impedance tomography (EIT)
Electromyography
Endothelial glycocalyx layer (EGL)
Endotracheal aspiration (ETA)
Esophagectomy
anesthesia
complications
anastomotic leak
anastomotic stricture
conduit ischemia
gastroesophageal reflux
postgastrectomy syndromes
indications
patient preparation
postoperative care
analgesia
blood administration
deep vein thrombosis prophylaxis
drainage tubes management
fluid management
nutrition considerations
physiotherapy
supplemental oxygen therapy
timing of extubation
preoperative selection
types
EV1000 TM /VolumeView TM system
Exercise-induced improvement
clinical data
experimental data
in muscle fiber phenotype
in oxygen transport components
Expiratory volume age diffusion (EVÁD) capacity score
Extracorporeal membrane oxygenation (ECMO)
advantages and disadvantages
components
heart-lung machine
iLA
impaired right ventricular function
CTEPH
extended lung surgery
PIPH
tracheobronchial surgery
indications
lung disease, impaired gas exchange
venoarterial
venovenous
Extravascular lung water (EVLW)
F
Fiber-optic bronchoscopy (FOB)
Flexible bronchoscopy
FloTrac TM /Vigileo TM system, 148–
Fluid management
AKI
ARDS
mortality rate
multiple-hit hypothesis
EGL
esophagectomy
fluid choice
goal-directed therapy
cardiac index estimation
pulmonary edema
PVV
SVV
hemodynamic monitoring
effectiveness
functional hemodynamic parameters
limitations
preload
systemic inflammatory response
impaired end-organ perfusion
lymphatics and RV dysfunction
postoperative ALI
classification
fluid administration
incidence
multiple-hit model
risk factors
pulmonary endothelial damage
Starling’s model
Fluid therapy
Forced expiratory volume in one second (FEV1)
Fraction of inspired oxygen (FiO 2 )
Functional conduit disorders
postgastrectomy syndromes
reflux
Functional residual capacity (FRC)
G
Gangrene
Gastroesophageal reflux
Global end-diastolic volume (GEDV)
Glycaemic control
H
Heart-lung machine (HLM)
Heat and moisture exchangers (HMEs)
Heated humidifiers (HHs)
Hemodynamic monitoring
blood lactate concentrations
blood pressure
cardiac output monitoring
PAC
pulse contour analysis
reasonable accuracy and precision
combining and integrating parameters
continuous arterial pressure invasive measurement
CVP
echocardiography
intravascular volume status
pericardial effusion
pulmonary embolism
thoracic trauma
valvular function
ventricular function
fluid management
effectiveness
functional hemodynamic parameters
limitations
preload
systemic inflammatory response
high-risk surgical patient definition
management strategies
perioperative fluid plan
proactive approach
reactive approach
step-by-step approach
system selection
venous oxygen saturation
Hemodynamic stress
Hemothorax
High-frequency jet ventilation (HFJV)
Humidification
Humidified high-flow nasal cannulas (HHFNC)
Hyperoncotic colloids
Hypokalemia
Hypothermia
Hypoxemia
Hypoxic vasoconstriction (HPV)
I
Immunosuppressive therapy
Incentive spirometry
Individual lung ventilation technique
Inflammatory mechanisms
Intercostal and interpleural block
Intercostal nerve block (ICNB)
Interventional lung assist (iLA)
Intrathoracic blood volume (ITBV)
Intravenous immunoglobulin (IVIG)
J
Juvenile myasthenia gravis (JMG)
L
LiDCO TM plus system
LiDCOTM rapid
Lobar torsion
Low-dose unfractionated heparin (LDUH)
Low molecular weight heparin (LMWH)
Lung volume reduction surgery (LVRS)
in COPD
uni/bilateral
M
Mechanical ventilation
air leak
bronchial blocker
chest tube placement
COPD
descending flow pattern
DLT
DLV
driving pressure
HFJV
inspired oxygen fraction
intraoperative and preoperative predictions
noisy pressure support ventilation
permissive hypercapnia
PLV
respiratory and non-respiratory complications
single-lumen tube
spontaneous breathing
tracheostomy
Univent® tube
weaning
Mortality Probability Model (MPM)
Multiple fractured ribs (MFR)
Muscle paralysis
Myasthenia gravis (MG)
AChR antibodies
antibody detection
cholinergic crisis
clinical classification
diagnosis and treatment approaches
edrophonium test
electromyography
incidence rate
MGFA
myasthenic crisis
pediatric/juvenile form
perioperative anesthetic management
age of disease onset
baseline train-of-four (TOF) ratio
JMG
mivacurium
postsynaptic nicotinic ACh receptors
pyridostigmine therapy
sevoflurane
sugammadex
VATET
volatile anesthetics
postoperative follow-up
postsynaptic muscle end plate
preoperative evaluation
therapy
Myasthenia gravis drug medication list (MGFA)
Myocardial Infarction and Cardiac Arrest (MICA)
N
National Surgical Quality Improvement Program (NSQIP)
Necrosis
Nerve injury
Neuromuscular blocking agents (NMBAs)
Noisy pressure support ventilation
Non-invasive positive pressure ventilation (NPPV)
acute cardiogenic pulmonary oedema
with acute exacerbation of COPD
advantages
ARDS
chronic respiratory failure
limitations and pitfalls
mechanism of action
pathophysiology
preventive use
therapeutic use
ventilation modes
CPAP
HHFNC
humidification
interfaces
PSV
Non-invasive ventilation (NIV)
See also Non-invasive positive pressure ventilation (NPPV)
absolute contraindications
administration
with chronic respiratory failure
COPD
postoperative pulmonary dysfunction
of ventilator support
Nonsteroidal anti-inflammatory drugs (NSAID)
NPPV
See Non-invasive positive pressure ventilation (NPPV)
Nutritional Risk Screening Score
O
Obstructive sleep apnea (OSA)
One-lung ventilation (OLV)
absolute and relative indications
anesthesia management
ARDS/ALI
ARMs
BAL fluid analysis
definition
end-inspiratory vs. end-expiratory airway pressure
FiO 2
general anesthesia
gravitational redistribution of blood
HPV
hypoxic pulmonary vasoconstriction
impaired gas exchange
indication
inhaled vasodilators
intravenous almitrine
management
oxygen
pathophysiological disturbances
patient position
PEEP
pressure-controlled ventilation
pro-inflammatory mediators
protective approach
pulmonary complications
rationale
recruitment maneuver
re-expansion pulmonary edema
tidal volumes
traditional approach
VCV vs. PCV
Open atrial septal defect
Oxygen therapy
P
PACU
See Postanesthesia care unit (PACU)
Pain management
clinical consequence
multimodal analgesia
physiology
preemptive analgesia
regional analgesia
continuous wound catheter analgesia
cryoanalgesia
intercostal and interpleural block
PVB
TEA
systemic analgesia
acetaminophen
gabapentin
ketamine
NSAID
opioids
pregabalin
selective alpha-2-adrenergic receptor agonist dexmedetomidine
treatment
Paravertebral block (PVB)
Penetrating trauma
Permissive atelectasis
Permissive hypercapnia
Persistent foramen ovale (PFO)
Physiological and operative severity score for the enumeration of mortality and
morbidity (POSSUM)
PiCCOplus TM /PiCCO2 TM system
Platypnea-orthodeoxia syndrome
Pleural effusion
Pneumonia
antibiotic prophylaxis
antibiotic treatment
bronchial colonization-airway colonization
cardiovascular complications
diagnosis
differential diagnosis
hypoventilation and ineffective cough
incidence
infectious complications
mortality rate
postoperative period
preoperative evaluations
pulmonary rehabilitation
risk factors
surgery related complications
thoracic analgesia
Pneumothorax
Positive end-expiratory pressure (PEEP)
Postanesthesia care unit (PACU)
central equipment
communications
discharge criteria
electrical power
environment
equipment and drugs
essential equipment
layout
lighting
medical gases
organization
bed slots
bed-spaces
emergency cart
location
square open-ward design
standard bright fluorescent ceiling lights
storage
traffic
patient monitoring
postoperative complications
air leak
bleeding
cardiovascular complications
chest x-ray
emergence delirium
pain
PONV
PORC
postoperative dysfunction
staff
Postgastrectomy syndromes
Postoperative care management
patient-related risk factors
age and frailty
ASA classification
cardiovascular risk scores
CCI
CPRI
lung function tests
NSQIP
pulmonary risk scores
S-MPM
postoperative triage
ACCM
APACHE score
local specificities
MPM
POSSUM
SAPS
SAS
procedure-related risk factors
anesthetic management
lung resections
muscle-sparing thoracotomy
postoperative complications
risk classification
thoracic surgical interventions
VATS
Postoperative cognitive disorder (POCD)
Postoperative hemorrhage
Postoperative myasthenic crisis (POMC)
Postoperative nausea and vomiting (PONV)
Postoperative pneumonia risk (PPR) index
Postoperative pulmonary complications (PPCs)
adverse pulmonary events
ARISCAT score
causes
CPRI
definitions
estimation
EVÁD score
incidence
observational studies
patient related risk factors
age
ASA classification
BMI
CHF
COPD
current alcohol use
diabetes mellitus
functional dependence
liver disease
low peripheral oxygen saturation
OSA
PFTs
preoperative anemia
preoperative hypoalbuminemia
renal disease
respiratory infection
respiratory symptoms
smoking
weight loss
patient stratification
POSSUM score
postoperative ARDS
PPR and PRF index
procedure-related and intraoperative risk factors
blood and blood products
duration of surgery
extent of lung resection
mechanical ventilation
muscle paralysis
restrictive vs. liberal fluid strategy
thoracotomy vs. median sternotomy
video-assisted thoracoscopic vs. open thoracic surgery
volatile vs. intravenous anesthetics
Postoperative residual curarisation (PORC)
Postoperative respiratory failure (PRF)
Post-pneumonectomy pulmonary edema (PPPE)
Postsurgical empyema
Postvagotomy diarrhea
PPCs
See Postoperative pulmonary complications (PPCs)
Pressure support ventilation (PSV)
Primary idiopathic pulmonary hypertension (PIPH)
Prolonged air leak (PAL)
Protected specimen brush (PSB)
Protective lung ventilation (PLV)
Pulmonary artery catheter (PAC)
Pulmonary contusion
clinical manifestations
endobronchial blockers
endotracheal intubation
FOB
NPPV
one-lung ventilation
outcomes
pulmonary parenchymal repair or resection
Pulmonary embolism (PE)
Pulmonary function tests (PFTs)
Pulmonary rehabilitation
Pulse contour analysis
calibrated devices
EV1000 TM /VolumeView TM system
LiDCO TM plus system
PiCCOplus TM /PiCCO2 TM system
uncalibrated devices
FloTrac TM /Vigileo TM system, 148–
LiDCO TM rapid
PulsioFlex TM system
Pulse pressure variation (PVV)
PulsioFlex TM system
Pyridostigmine therapy
R
Rehabilitation
exercise types
physical fitness
aerobic
causes
clinical data
CPET
exercise training programs
experimental data
in muscle fiber phenotype
oxygen cascade
in oxygen transport components
self-report questionnaires
stress-and inactivity-induced muscle wasting
and prohabilitation
Residual hemothorax
Respiratory infection
Revised Cardiac Risk Index (RCRI)
Rib fractures
acute pain management, MFR
ICNB
interpleural block
TEA
TPVB
Robotic surgery
S
Segmental torsion
Simple motion detectors
Simplified Acute Physiology Score (SAPS)
Spontaneous sputum method
Stroke volume variation (SVV)
Subcutaneous emphysema (SE)
Subjective Global Assessment
Surgical Apgar Score (SAS)
Surgical Mortality Probability Model (S-MPM)
T
Tacrolimus
Thoracic epidural analgesia (TEA)
Thoracic paravertebral block (TPVB)
Thoracic Revised Cardiac Risk Index (ThRCRI)
Thoracic trauma
hemothorax
penetrating and blunt traumas
pneumothorax
pulmonary contusion
clinical manifestations
endobronchial blockers
endotracheal intubation
FOB
NPPV
one-lung ventilation
outcomes
pulmonary parenchymal repair or resection
rib fractures
acute pain management, MFR
ICNB
interpleural block
TEA
TPVB
Thoracotomy
Three-bottle chest drainage system
Thromboprophylaxis
general measures
mechanical methods
pharmacological methods
rationale
Tracheobronchial resection
Tracheobronchial surgery
Tracheostomy
Transesophageal echocardiography (TEE)
See Echocardiography
Transfusion-related acute lung injury (TRALI)
Transpulmonary thermodilution technology
Transthoracic echocardiography (TTE)
See Echocardiography
Two-lung ventilation (TLV)
V
Valvular function
Vascular anastomotic complications
Venous thromboembolism (VTE)
Ventricular arrhythmia
Video-assisted surgery (VATS)
Video-assisted thoracoscopic extended thymectomy (VATET)
Vitamin K antagonists (VKA)
W
Weaning

Postoperative Care in Thoracic Surgery A Comprehensive Guide

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Postoperative Care in Thoracic Surgery A Comprehensive Guide

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Editors

Mert Şentürk and Mukadder Orhan Sungur

Postoperative Care in Thoracic Surgery

Mukadder Orhan Sungur

ISBN 978-3-319-19907-8 e-ISBN 978-3-319-19908-5

Library of Congress Control Number: 2017933454

© Springer International Publishing Switzerland 2017

The use of general descriptive names, registered names, trademarks, service

Printed on acid-free paper

2 Where Should I Send My Patient After the Operation?​

3 Does It Matter How I Ventilate the Patient During the Operation?​

4 Can Postoperative Pulmonary Complications Be Objectively Evaluated?​

5 Fluid Management During and After the Operation:​ Less Is More or

6 How to Organise the PACU?​ What to Treat in the PACU?​

7 Should I Blame the Surgeon:​ Surgical Complications and Surgical

8 Should Every “Myasthenic Thymectomy” Be Sent to ICU?​

9 How About Esophagectomies?​

10 Do the New Hemodynamic Monitoring Devices Make Sense Compared to

11 What Are the Specific Challenges in the Postoperative Mechanical

13 Lung Surgery and Extracorporeal Oxygenation

14 Pneumonia After Thoracic Surgery

15 When and How Do I Have to Treat the Arrhythmias After Thoracic

16 Management of Antiaggregated and Anticoagulated Patients Scheduled

17 Pain Management Following Thoracic Surgery

18 Rehabilitation for Thoracic Surgical Patients:​ Why, When, and How

19 Perioperative Care of Thoracic Trauma Patient

20 Chronic Obstructive Pulmonary Disease and the Postoperative Period

Marcelo Gama de Abreu

Marc Joseph Licker

Perihan Ergin Özcan

Giorgio Della Roca

Mukadder Orhan Sungur

Laszlo L. Szegedi, MD, PhD

1. What Happens to the Lung During

1.2 Airway Closure

1.3 Formation of Atelectasis

1.4 Prevention of Atelectasis

Positive end-expiratory pressure

Oxygen and atelectasis during induction of anesthesia

Avoiding the preoxygenation procedure and ventilating with 30 % instead of 100

Oxygen and atelectasis during anesthesia

Oxygen and atelectasis during emergence from anesthesia

1.5 Individual Lung Ventilation

3. Two ventilators were used

1.6 One-Lung Ventilation

As with conventional two-lung ventilation, there is no generally accepted

2. Futier E, Constantin JM, Paugam-Burtz C, Pascal J, Eurin M, Neuschwander A et al (2013) A trial of

4. Serpa Neto A, Hemmes SN, Barbas CS, Beiderlinden M, Fernandez-Bustamante A, Futier E et al

6. Tokics L, Strandberg A, Brismar B, Lundquist H, Hedenstierna G (1987) Computerized tomography of

10. Damgaard-Pedersen K, Qvist T (1980) Pediatric pulmonary CT-scanning. Anaesthesia-induced

18. Reinius H, Jonsson L, Gustafsson S, Sundbom M, Duvernoy O, Pelosi P et al (2009) Prevention of

Rothen HU, Sporre B, Engberg G, Wegenius G, Reber A, Hedenstierna G (1995) Prevention of

25. Rusca M, Proietti S, Schnyder P, Frascarolo P, Hedenstierna G, Spahn DR et al (2003) Prevention of

27. Edmark L, Auner U, Hallen J, Lassinantti-Olowsson L, Hedenstierna G, Enlund M (2014) A ventilation

28. Hedenstierna G, Baehrendtz S, Klingstedt C, Santesson J, Soderborg B, Dahlborn M et al (1984)

30. Darowski M, Hedenstierna G, Baehrendtz S (1985) Development and evaluation of a flow-dividing

37. Kozian A, Schilling T, Schutze H, Senturk M, Hachenberg T, Hedenstierna G (2011) Ventilatory

44. Trachsel S, Hambraeus-Jonzon K, Bergquist M, Martijn C, Chen L, Hedenstierna G (2015) No

2. Where Should I Send My Patient After

A clinician’s judgment on postoperative triage is largely based on predicting

2.2 Risk Stratification

2.2.1.2 Cardiovascular Risk Scores

Table 2.3 Thoracic Revised Cardiac Risk Index (ThRCRI)

2.2.1.3 Pulmonary Risk Scores

2 Where Should I Send My Patient After the Operation?

3 Does It Matter How I Ventilate the Patient During the Operation?

4 Can Postoperative Pulmonary Complications Be Objectively Evaluated?

5 Fluid Management During and After the Operation: Less Is More or

6 How to Organise the PACU? What to Treat in the PACU?

7 Should I Blame the Surgeon: Surgical Complications and Surgical

8 Should Every “Myasthenic Thymectomy” Be Sent to ICU?

9 How About Esophagectomies?

18 Rehabilitation for Thoracic Surgical Patients: Why, When, and How